Author Archives: Fredricko

Text of IOM Responses to Questions About Selection of Its CIRM Witnesses

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Here is the text of the questions posed this week by the California Stem Cell Report to the Institute of Medicine concerning its performance assessment of the $3 billion California stem cell agency and the IOM hearing Jan. 24 in San Francisco.

Also included is the text of the responses from the IOM, which is being paid $700,000 by the agency to conduct the study. The initial question was addressed to Harold Shapiro, chairman of the IOM-CIRM panel. Christine Stencel, senior media relations officer for the IOM, replied. The second question was addressed directly to Stencel.

Here are the questions sent Jan. 16 to Shapiro.

"Dr. Shapiro --

"I am working on an  article dealing with the upcoming meeting of the CIRM IOM panel Jan. 24. It will discuss the topics to be discussed and the witnesses. I would like your comments particularly in regard to the selection of the witnesses.

"Other than CIRM-connected individuals and media representatives(based on the agenda as of Jan. 16), they come from institutions that have received $356 million from the stem cell agency. Several of them have personally received grants. (UC Davis representatives were later added to the agenda, boosting the figure from $356 million to $418 million.)

"My questions:
"How were these witnesses selected? Does the IOM actually expect to receive forthright assessments of CIRM from individuals that have received hundreds of millions of dollars from the agency?

"Why weren't representatives from other well-informed California organizations invited, such as the Little Hoover Commission, which performed a lengthy study of CIRM, and the Center for Genetics and Society, which has followed CIRM since 2004.?  Are there any plans to seek them out for public comment?

"Why is 50 percent of the meeting being held behind closed doors? Who is expected to testify? What will be the nature of the business to be discussed? CIRM is a public enterprise, engaged in spending $6 billion (including interest) of taxpayer funds. It would seem that almost nothing that it does should be  barred from public scrutiny.

"Finally, who is Larry Fisher? He is listed on the IOM agenda as having a connection with the Los Angeles Times. However, an employee of the Times tells me that Fisher is not listed in any of the directories that he has access to.

"Dr. Shapiro, I will carry any comments that you make verbatim on the California Stem Cell Report. If you would like to add more than responses to the questions, I would welcome your thoughts."

Here is the response Jan. 17 from Stencel.

"Dr. Shapiro forwarded your query to the IOM for response. Our offices were closed yesterday for the MLK holiday, so we are catching up on all the correspondence we’ve received. The upcoming meeting is one of several means by which the committee will gather information and perspectives to inform its deliberations. The list of presenters and topics you see on the agenda reflect information and insights that the committee considered useful at this point in its work. This meeting is not the sole means by which committee members will gather information. For example, you will note that there are links to surveys posted on the project page (http://www.iom.edu/Activities/Research/CIRMReview.aspx) on the IOM website that request information from a variety of sources. The committee has also requested specific data from CIRM; a list of what was requested is in the Public Access File for this study, which is accessible via the Public Access Records Office. In addition, the committee expects to hold another information gathering meeting in California later this year.

"To your query about the extent to which the meeting is open, the committee is holding a day-long open meeting to gather information on Jan. 24. The closed portion of the meeting will be devoted to internal committee discussions; there will be no presentations. This is per the National Academies study process. Please see Stage 3 in the explanation of the National Academies study process on this webpage: http://www.nationalacademies.org/studyprocess/index.html. 

"To your question about Mr. Fisher, due to an oversight in drafting the agenda, he is misidentified as being affiliated with the LA Times. As the agenda you last saw indicated, he was an invited speaker, but since he has not responded, he will not be speaking at the meeting and is being removed from the agenda.

"Thank you for your ongoing interest in this IOM review."

Here are the California Stem Cell Report questions Jan. 17 to Stencel:

"I understand that some members of the CIRM - IOM panel made a publicly unannounced trip to California to visit some recipient institutions. What was the purpose of the trip? Who went? How long did it last? What institutions were visited? Who put together the agenda for the visit? Was it at the invitation of CIRM and facilitated by CIRM? Did the traveling members of the panel meet with any representatives of institutions or groups that have not received CIRM funds? Please feel free to add any other thoughts on this subject if you wish. Thank you."

Here is Stencel's response:

"Harold Shapiro and Terry Magnuson, who had been asked to serve as chair and vice chair of the committee, visited CIRM and two universities conducting stem cell research in September 2011 before the full committee was assembled.  Drs. Shapiro and Magnuson wanted to visit CIRM to gain a better understanding of the task that their committee, when formed, would be undertaking given the many questions being posed (per Statement of Task) and the limited timeframe to complete the review. They also met with leaders of Stanford and the University of California, San Francisco and toured laboratories on the two campuses to get a better feel for the type of stem cell research supported by CIRM. IOM study director Adrienne Stith Butler accompanied them."

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

California Stem Cell Agency Slated for More Bond Funding This Spring

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The California stem cell agency is slated to secure additional bond funding this spring when the financially troubled Golden State initiates a new round of borrowing.

CIRM Chairman Jonathan Thomas told directors today that the $3 billion agency will be involved  in the upcoming round. He did not specify the amount that CIRM would receive or the timing of the bond issue.

The agency's only significant funding comes from state bonds, whose funds flow directly to CIRM. The governor and legislature cannot touch the CIRM funds under the terms of the ballot measure that created the research effort in 2004.

Last year at this time, the state suspended bond sales. At the time, CIRM had sufficient funds to meet its commitments until about June of this year. Late last year, Thomas worked out a temporary funding arrangement with the governor's financial aides to cover any possible shortfall.

Thomas made the announcement at the beginning of today's CIRM board meeting in San Diego.

Currently CIRM President Alan Trounson is reviewing new stem cell research that has been published recently.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Two Potential Buyers Eyeing Geron's hESC Business

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Geron has two interested potential buyers for its human embryonic stem cell business, the president of the California stem cell agency said today.

Alan Trounson told CIRM directors that at one point four parties had expressed interest  but two have backed out. He did not disclose the names of any of the parties.

Last fall, Geron announced it was giving up its hESC work because of financial concerns about what once was the first clinical trial of a human embryonic stem therapy. Last summer CIRM loaned Geron $25 million for the trial, which has been repaid with interest.  Following Geron's announcement, Trounson said he was working to help find a buyer for Geron's hESC business.

However, today he said he was "suddenly distanced" from the process a few days ago. CIRM director Sherry Lansing, who once headed a Hollywood film studio, asked Trounson whether there was anything that directors could do to help find a buyer for Geron's hESC business. She asked about the amount of money needed by Geron and whether patient advocates could help generate other momentum.

Trounson suggested that the discussion should  be continued privately. He did say that CIRM has prepared a document that outlines what would  be necessary for the agency to resume funding of the hESC trial.

Trounson told directors that Geron's departure from hESC research has had "a very strong negative influence internationally."

Geron, which is based in Menlo Park in California, said last week it has hired Stifel Nicolaus & Co. to help sell the hESC business. . 

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Two Potential Buyers Eyeing Geron’s hESC Business

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Geron has two interested potential buyers for its human embryonic stem cell business, the president of the California stem cell agency said today.

Alan Trounson told CIRM directors that at one point four parties had expressed interest  but two have backed out. He did not disclose the names of any of the parties.

Last fall, Geron announced it was giving up its hESC work because of financial concerns about what once was the first clinical trial of a human embryonic stem therapy. Last summer CIRM loaned Geron $25 million for the trial, which has been repaid with interest.  Following Geron's announcement, Trounson said he was working to help find a buyer for Geron's hESC business.

However, today he said he was "suddenly distanced" from the process a few days ago. CIRM director Sherry Lansing, who once headed a Hollywood film studio, asked Trounson whether there was anything that directors could do to help find a buyer for Geron's hESC business. She asked about the amount of money needed by Geron and whether patient advocates could help generate other momentum.

Trounson suggested that the discussion should  be continued privately. He did say that CIRM has prepared a document that outlines what would  be necessary for the agency to resume funding of the hESC trial.

Trounson told directors that Geron's departure from hESC research has had "a very strong negative influence internationally."

Geron, which is based in Menlo Park in California, said last week it has hired Stifel Nicolaus & Co. to help sell the hESC business. . 

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Stem Cell Agency Shying Away From Another Multibillion-dollar Bond Proposal

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The $3 billion California stem cell agency, which is expected to run out of cash in five years, is backing away from an attempt to win voter approval of another multibillion dollar bond measure to finance its research efforts.

The agency disclosed its new position in a document posted in connection with the meeting tomorrow of its governing board in San Diego. CIRM said,

"Although additional funding could be a possibility in the future, it would be premature even to consider another bond measure at this time. Instead, CIRM should focus its efforts on creating a platform that enables others to carry on CIRM’s work."

The statement is a sharp departure from previous discussion of mounting a ballot campaign for a $4 billion to $5 billion bond measure on behalf of CIRM.

The only significant source of cash for the agency currently is the $3 billion in bonds approved by voters in 2004. Nearly half of that is committed. The latest financial report from CIRM shows its funding of research peaking in 2017-18.

During the last year or so, former CIRM Chairman Robert Klein has repeatedly discussed another bond measure and has even more recently expressed his desire to raise funds for a new electoral campaign. Klein resigned from his post last June. The CIRM board elected Jonathan Thomas, a Los Angeles bond financier, to replace Klein, who was the agency's first chairman and who led the 2004 ballot campaign.

In 2010, the CIRM board approved spending $700,000 for an Institute of Medicine study of CIRM with the expectation that its findings would enhance the likelihood of approval of more bond funding.

The IOM study is currently underway. The blue-ribbon panel is scheduled to hold a two-day public meeting in San Francisco Jan. 24-25 as part of its assessment of CIRM performance.

CIRM largely functions below the news media's radar, but talk of a new pitch for money has triggered negative commentary. Last month, the San Jose Mercury News said in an editorial that the agency should close its doors when its cash runs out because another bond measure would siphon off much-needed money for education and other critical services already "starved" by state budget cuts.

Backing away from another bond measure could benefit CIRM by helping to remove the likelihood that its actions will be judged in the context of an electoral campaign. But the action also raises the possibility that some of CIRM's best employees may leave for better prospects given that they may not have much of a future at an agency that would appear to be going out of business – at least at its current robust level.

The CIRM document dealing with the bond measure is dubbed a "transition plan" and is required by state law.

Instead of seeking to borrow more billions, the document said,

"CIRM should focus its efforts on creating a platform that enables others to carry on CIRM’s work. Through its funding of state of the art research facilities, collaborative funding agreements, and industry engagement, CIRM has already made progress in creating this platform."

The document also raised the possibility of creation of a nonprofit organization to carry on CIRM's stem cell research, a proposal that has floated quietly for some years. Such an effort could involve raising funds from the biotech industry, which CIRM is currently trying to engage in a more friendly way.

At the top of CIRM's list of transition plan activities is creation -- both nationally and internationally -- of "Alpha Stem Cell Clinics" for delivery of therapies to patients. The clinics also would foster clinical trials and evaluate cell therapies. Additionally included are efforts to drive "follow-on funding" for CIRM projects and strengthened efforts to support industry.

Directors could alter the CIRM transition plan at their meeting tomorrow. But it was placed on the agenda by Chairman Thomas and is unlikely to see major revisions.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

Prealgebra Tutor in Richmond – Richmond Virginia (23236)

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Prealgebra Tutor in Richmond

Passion: Helping students understand and enjoy a subject area is my passion. I live for the "aha" moment when they "get it" for the first time and that day when I have a formerly math-hating or math-a-phobic student smiling and laughing as they work.

Prealgebra tutor in richmondExperience: I worked in the drop-in tutoring center during community college tutoring all math through Calc I, English/Writing, and Speech/Communications. I also worked at a Kumon Math and Reading center with students as young as kindergarten and have worked as a freelance tutor for math, general study skills/all subjects with clients ranging from Junior High School students in need of remedial help to older adult graduate students returning to math or stats after many years. I have worked with students from public, private, and homeschool backgrounds successfully and make sure to keep parents "in the loop" as full partners invested in the student's learning. I have also taught 4-H dog training classes before – nothing phases me after fifteen 8-16 year old 4-H members with their completely untrained dogs show up on the first night! Training dogs and teaching kids to train them has taught me a great deal about how we learn and how to motivate learning.

Further Qualifications: I earned a double-degree in Mathematics and Cognitive Science (the study of how we think, learn, process, remember, and solve problems) with a 3.9+ GPA and am currently in a Master's program studying Mathematics and teaching undergraduate mathematics courses. My future goal is to teach community college and to research the cognitive processes and pedagogy of teaching mathematics.

Contact me

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SAT Reading Tutor in Richmond – Richmond Virginia (23236)

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SAT Reading Tutor in Richmond

Sat Reading Tutor RichmondI am a magna cum laude college graduate with a BA in history and a VA secondary social studies teaching license. Though I am not certified to teach English, I have extensive experience as a paid writing tutor, and my Middle School English Praxis II scores qualify me to teach English under certain conditions. More importantly than the above qualifications, I really love working with kids, both on an academic level and informally. As a tutor, my preliminary goal is, of course, to improve my students' understanding of the material in order to improve their grades. However, I find little lasting value in improved grades if there is not a corresponding increase in self confidence/perseverance and intellectual curiosity. Of course, few students love every subject they study. I have never loved math and always found it hard to earn good grades in such classes. However, I have learned to appreciate its intrinsic value and through my struggles with it, I have gained greater confidence and learned perseverance. I hope to teach my students about the intrinsic value of English and history and about the great value in setting and achieving difficult goals. I want to do this by genuinely getting to know my students — understanding how they think, what motivates and interests them, and who they are as individuals inside and outside the classroom. I believe that if I can understand your student as a person, not just as a GPA or learning disability (for example), then I can point them to the ways in which English and history can be important to them as an individual. I also believe that tutors should learn as much from their students as they teach. This requires patience, humility, and a listening ear, as well as good preparation and a thorough knowledge base, all of which are qualities that I will strive to have as a tutor for your student.

Contact me

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The Very End of Aging is Quite Different From Being Merely Old

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We can understand aging as being an accumulation of damage - of various types - to the biological machinery in and between our cells. This proceeds in an accelerating fashion as it passes various thresholds, and prompts evolved systems and feedback loops in our biology to flail, try to compensate, or fail in cascades. But in the very late stages of aging, for the oldest old, things stop being quite so easy to frame, and relationships between functional components that hold throughout the rest of live cease or change dramatically. We see some of this change of phase in aging at work in the mortality plateau of flies - the risk of death per unit time in very old flies simply stops increasing, which poses interesting questions given that they are still alive and therefore presumably still accumulating biological damage. There are some signs that this late-life plateau of mortality rate might also exist in humans - but by no means enough data to be confident in that.

Here are a couple of papers from the Rejuvenation Research advance publication queue that also point towards the interesting nature of the late stages of aging. The first one is eye-opening, given everything we know about the effects of exercise at all other stages of life.

Physical Activity and Cardiac Function in the Oldest Old

The relationship of physical activity (PA) and cardiac function in the oldest old remains unclear. The objective of this study was to evaluate the relationship between PA and cardiac structure and function, in the oldest old. Subjects were recruited from the Jerusalem Longitudinal Cohort Study that was initiated in 1990 and has followed an age homogeneous cohort of Jerusalem residents born in 1920-1921. ... After adjusting for sex, education, diabetes, ischemic heart disease, hypertension, dependence in activities of daily living, and body mass index (BMI), no significant associations were found between systolic or diastolic function, or left ventricular structure and PA. Gender-specific analyses yielded similar findings. Our study of the oldest old did not demonstrate an association between PA and cardiac structure or function.

Paradoxical Physiological Transitions from Aging to Late Life in Drosophila

In a variety of organisms, adulthood is divided into aging and late life, where aging is a period of exponentially increasing mortality rates and late life is a period of roughly plateaued mortality rates. In this study we used 57,600 Drosophila melanogaster from six replicate populations to examine the physiological transitions from aging to late life in four functional characters that decline during aging: desiccation resistance, starvation resistance, time spent in motion, and negative geotaxis. Time spent in motion and desiccation resistance declined less quickly in late life compared to their patterns of decline during aging. Negative geotaxis declined at a faster rate in late life compared to its rate of decline during aging.

These results yield two key findings: (1) Late-life physiology is distinct from the physiology of aging, in that there is not simply a continuation of the physiological trends which characterize aging; and (2) late life physiology is complex, in that physiological characters vary with respect to their stabilization, deceleration, or acceleration in the transition from aging to late life. These findings imply that a correct understanding of adulthood requires identifying and appropriately characterizing physiology during properly delimited late-life periods as well as aging periods.

I would like to see the advent of a world in which this sort of knowledge is a mere curio, as no-one ever experiences the final stages of degenerative aging, nor indeed does anyone even become what we'd now call old, aged, over the hill. Long lives, but no decline in vigor or health. That is a world in which the SENS research program has succeeded, and everyone has the opportunity to undergo periodic repair of metabolism, mitochondria, stem cells, and removal of harmful aggregates - no more remarkable than flu shots today.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Looking for Evidence of Inherited Longevity in Cells

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Researchers are examining cellular biochemistry in people who belong to long-lived families: "The offspring of nonagenarian siblings suffer less from age related conditions and have a lower risk of mortality compared to their partners. Fibroblast strains derived from such offspring in middle age show different in vitro responses to stress, more stress-induced apoptosis and less senescence when compared to strains of their partners. Aiming to find differences in cellular metabolism in vitro between these fibroblast strains, [cells were] analysed using (1)H nuclear magnetic resonance (NMR)-based metabolic footprinting. ... Strains from offspring and their partners were compared ... The ala-gln and glucose consumption were higher for fibroblast strains derived from offspring when compared to strains of their partners. Also, production of glutamine, alanine, lactate and pyroglutamic acid was found to be higher for fibroblast strains derived from offspring. In conclusion, differences in NMR-based metabolic profiles of human cells in vitro reflect the propensity for human longevity of the subjects from whom these were derived."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22218423

Source:
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Investigating How Stem Cell Transplants Assist Healing in the Brain

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Via EurekAlert!: "For years, researchers seeking new therapies for traumatic brain injury have been tantalized by the results of animal experiments with stem cells. In numerous studies, stem cell implantation has substantially improved brain function in experimental animals with brain trauma. But just how these improvements occur has remained a mystery. Now, an important part of this puzzle has been pieced together by researchers ... In experiments with both laboratory rats and an apparatus that enabled them to simulate the impact of trauma on human neurons, they identified key molecular mechanisms by which implanted human neural stem cells - stem cells that are in the process of developing into neurons but have not yet taken their final form - aid recovery from traumatic axonal injury. A significant component of traumatic brain injury, traumatic axonal injury involves damage to axons and dendrites, the filaments that extend out from the bodies of the neurons. The damage continues after the initial trauma, since the axons and dendrites respond to injury by withdrawing back to the bodies of the neurons. ... Axons and dendrites are the basis of neuron-to-neuron communication, and when they are lost, neuron function is lost. In this study, we found that our stem cell transplantation both prevents further axonal injury and promotes axonal regrowth, through a number of previously unknown molecular mechanisms. ... We identified about 400 proteins that respond differently after injury and after grafting with neural stem cells. ... a group of cytoskeleton proteins was being changed, and in particular one called alpha-smooth muscle actin, which had never been reported in the neurons before.""

Link: http://www.eurekalert.org/pub_releases/2012-01/uotm-slh011212.php

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Another Update on a Tissue Engineered Trachea Transplant

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One of the world's more active tissue engineering research and development groups works on building replacement tracheas from a scaffold and the patient's own cells. They have carried a number of successful transplants in recent years, and seem on a par with Tengion's work on bladders, or the folk producing heart valves for children in terms of outcomes and technological sophistication.

Here's an update on a transplant carried out late last year:

Surgeons in Sweden have replaced the cancerous windpipe of a Maryland man with one made in a laboratory and seeded with the man's cells.

...

"What we did is surgically remove his malignant tumor," Dr. Macchiarini said. "Then we replaced the trachea with this tissue-engineered scaffold." The Y-shaped scaffold, fashioned from nano-size fibers of a type of plastic called PET that is commonly used in soda bottles, was seeded with stem cells from Mr. Lyles's bone marrow. It was then placed in a bioreactor - a shoebox-size container holding the stem cells in solution - and rotated like a rotisserie chicken to allow the cells to soak in.

After two of days, it was installed in Mr. Lyles during an elaborate operation in which it was sutured to his throat and lungs. All told, the treatment cost about $450,000, Mr. Lyles said.

...

Dr. Macchiarini has performed a dozen trachea transplants since 2008, but the first 10 used organs from cadavers in which all the living cells were removed, leaving behind a natural scaffold of cartilage. Donated tracheas are rare, however, and are never a perfect fit. In Mr. Lyle's case, and in the case of an Eritrean man who received a similar transplant last June and is doing well, the synthetic scaffold is made using CT scans of the existing trachea to ensure it matches precisely.

The cost of the first tissue engineered parts will fall dramatically once the procedures become more widespread and the underlying technologies more robust and commoditized. But costs will not fall as far is they would in an actual free market in medicine, and there will be long and unnecessary years of delay - and vast expense for the sponsoring companies - before regulators in wealthy Western countries will approve these new applications of cell science for broad use.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Regeneration Observed in Kidney Podocyte Cells

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Another cell population thought to be static throughout life turns out to be capable of regeneration and renewal, given the right cues: "Damage to podocytes - a specialized type of epithelial cell in the kidney - occurs in more than 90 percent of all chronic kidney disease. Now researchers [have] uncovered an unexpected pathway that reveals for the first time how these cells may regenerate and renew themselves during normal kidney function. ... Podocytes are found only in the kidney and are an integral structural component of its blood-filtering system. They stand shoulder-to-shoulder in a part of the organ called the glomerulus and wrap their long 'feet' around the semi-permeable capillaries through which blood flows. Narrow slits between the feet allow small molecules, such as water and salts, to pass while blocking large proteins. This filtering process is the first step to forming urine, and it is critically important - even one missing cell can leave a gap that would allow unwanted molecules through the barrier. ... It used to be thought that you were born with podocytes, and you died with the same podocytes - you don't make any more during your lifetime. ... The problem was, such a scenario doesn't make a lot of evolutionary sense - particularly when other epithelial cells routinely regenerate themselves. ... Podocytes may utilize recognized pathways of regeneration to renew themselves throughout life, [and] people suffering from chronic kidney disease may simply have worn out or outpaced their podocytes' capacity for renewal ... Now that the researchers know podocytes have the ability to regenerate in response to common cellular signals, their next step is to learn whether this regeneration occurs in healthy animals and people. ... If we can harness this regeneration, we may one day be able to treat people with chronic kidney disease."

Link: http://www.sciencedaily.com/releases/2011/12/111205102706.htm

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From the Programmed Aging Camp

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Here is an open access paper from a researcher who focuses on mTOR and sees aging as almost entirely programmed, not the consequence of stochastic damage. His view as outlined in the paper is analogous to the view of nuclear DNA damage as not being significant over the present human life span. I think he has a very large hill of evidence for the damage-based view of aging to overcome in order to make a convincing point, however, and this should serve as a reminder that there are a great many diverse (but not necessarily well supported) views in the scientific community when it comes to the nuts and bolts of aging: "Aging is defined as a decline caused by accumulation of all sorts of damage, in particular, molecular damage. This statement seemed so obvious that it was not questioned. Yet several lines of evidence rule out molecular damage as a cause of aging. Yes, of course, molecular damage accumulates over time. But this accumulation is not sufficient to cause organismal death. Eventually it would. But the organism does not live long enough, because another cause terminates life first. This cause is aging, a continuation of developmental growth. Definitely, developmental growth is not driven by accumulation of molecular damage, although molecular damage accumulates. Similarly, aging is not driven by damage. Growth is stimulated in part by mitogen- and nutrient-sensing (and other) signaling pathways such as mTOR. Aging, 'an aimless continuation of developmental program', is driven by the same signaling pathways including mTOR. Aging in turn causes damage: not molecular damage but non-random organ damage (stroke, infarction, renal failure and so on) and death. Seemingly, one objection to this concept is that cancer is caused by molecular damage. And cancer is often a cause of death in mammals. So how may one claim that damage does not drive aging, if it is involved in cancer. Let us discuss this."

Link: http://impactaging.com/papers/v3/n12/full/100422.html

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