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Stem cells
Placenta cell focus of potential new treatment(06/05/15)
A study, Human Placenta-Derived Cells (PDA-001) For The Treatment Of Adults With Multiple Sclerosis: A Randomised, Placebo-Controlled, Multiple-Dose Study, published in the journal Multiple Sclerosis and Related Disorders and led by researchers at Mount Sinai in New York and Celgene Cellular Therapeutics, has revealed an infusion based on cells derived from the placenta proved to be safe for patients with multiple sclerosis and a promising new treatment for the condition.
It has been previously shown that therapeutic cell-based infusions have an immunomodulatory and repair action in MS. PDA-001 in particular is a preparation of cultured mesenchymal-like cells derived from healthy human placental tissue and designed for the treatment of MS as these cells have immunomodulatory, anti-inflammatory, pro-regenerative and neuroprotective properties. As these placenta cells are expanded in cell culture, one healthy donor is capable of supplying enough cells for several patients.
In the study, researchers tested the safety and possible exacerbation of the disease with this new MS treatment approach based on PDA-001. A phase 1b, randomised, multi-centre, double-blind, placebo-controlled study was conducted with 16 MS patients (ten with relapsing-remitting MS and six with secondary progressive MS), aged between 18 and 65 years. Six patients received a high dose of PDA-001 (600×106 cells), other six were given a lower dose (150×106 cells), and the remaining four patients received a placebo. Patients were monitored monthly for brain lesions.
Researchers found none of the patients had worsening of MS-related brain lesions one year after treatment with both PDA-001 doses, and the majority of the patients had stable or had improved levels of disability.
"We're hoping to learn more about how placental stromal cells contribute to myelin repair," said the study's lead author and Professor of Neurology at Mount Sinai, Dr Fred Lublin in a news release.
"We suspect they either convert to a myelin making cell, or they enhance the environment of the area where the damage is to allow for natural repair. Our long-term goal is to develop strategies to facilitate repair of the damaged nervous system."
The research team concluded that PDA-001 treatment was overall safe and well tolerated by patients, and that preliminary evidence suggests that PDA-001 could be able to repair damaged nerve tissues in MS patients.
"This is the first time placenta-derived cells have been tested as a possible therapy for multiple sclerosis," said Dr Lublin.
"The next step will be to study larger numbers of MS patients to assess efficacy of the cells, but we could be looking at a new frontier in treatment for the disease."
Source: Multiple Sclerosis News Today © BioNews Services 2015 (06/05/15)
Athlete's foot cream 'could repair nerve damage'(21/04/15)
A common athlete's foot cream sold over the counter at most chemists could help people living with multiple sclerosis, a new study claims.
Researchers believe the drug miconazole - the active ingredient in Daktarin - instructs stem cells in the brain to repair nerve damage. The discovery comes after a team at Case Western Reserve University in Ohio tested more than 700 drugs to see if anyone would be useful against MS.
The athlete's foot drug and a cream used to treat eczema were found to stimulate the regeneration of damaged brain cells. It was found to reverse paralysis in mice.
"We know that there are stem cells throughout the adult nervous system that are capable of repairing the damage caused by multiple sclerosis, but until now we had no way to direct them to act," said Dr Paul Tesar, Professor of Innovative Therapeutics at Case Western Reserve School of Medicine.
"Our approach was to find drugs that could catalyse the body's own stem cells to replace the cells lost in multiple sclerosis."
The team said that much work remains before multiple sclerosis patients might benefit from the promising approach.
Scientists still must find ways to transform the medications for internal use and determine their long-term efficacy and potential side effects.
However they said the initial findings show promise and the drugs have been shown to work on human stem cells.
"This truly represents a paradigm shift in how we think about restoring function to multiple sclerosis patients," said Dr Robert Miller of the neurosciences faculty.
"The drugs we identified are able to enhance the regenerative capacity of stem cells in the adult nervous system. It showed a striking reversal of disease severity in the mice."
The research was published in the journal Nature.
Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (21/04/15)
'Miracle' stem cell therapy reverses multiple sclerosis(02/03/15)
A pioneering new stem cell treatment is allowing people with multiple sclerosis to walk, run and even dance again, in results branded 'miraculous' by doctors.
Patients who have been wheelchair-bound for 10 years have regained the use of their legs in the groundbreaking therapy, while others who were blind can now see again.
The treatment is the first to 'reverse' the symptoms of MS, which has no cure, and affects around 100,000 people in Britain.
The two dozen patients who are taking part in the trials at the Royal Hallamshire Hospital in Sheffield and Kings College Hospital, London, have effectively had their immune systems 'rebooted'.
Although it is unclear what causes MS, some doctors believe that it is the immune system itself which attacks the brain and spinal cord, leading to inflammation and pain, disability and in severe cases, death.
In the new treatment, specialists use a high dose of chemotherapy to knock out the immune system before rebuilding it with stem cells taken from the patient's own blood.
Stem cells are so effective because they can become any cell in the body based on their environment.
"Since we started treating patients three years ago, some of the results we have seen have been miraculous," Professor Basil Sharrack, a consultant neurologist at Sheffield Teaching Hospitals NHS Foundation Trust, told The Sunday Times.
"This is not a word I would use lightly, but we have seen profound neurological improvements."
During the treatment, the patient's stem cells are harvested and stored. Then doctors use aggressive drugs which are usually given to cancer patients to completely destroy the immune system.
The harvested stem cells are then infused back into the body where they start to grow new red and white blood cells within just two weeks.
Within a month the immune system is back up and running fully and that is when patients begin to notice that they are recovering.
Holly Drewry, 25, of Sheffield, was wheelchair bound after the birth of her daughter Isla, now two, but she claims the new treatment has transformed her life.
"It worked wonders," she said. "I remember being in the hospital... after three weeks, I called my mum and said: 'I can stand'. We were all crying.
"I can run a little bit, I can dance. I love dancing, it is silly but I do. I enjoy walking my daughter around the park in her pram. It is a miracle but I can do it all."
However specialists warn that patients need to be fit to benefit from the new treatment.
"This is not a treatment that is suitable for everybody because it is very aggressive and patients need to be quite fit to withstand the effects of the chemotherapy," warned Prof Sharrack.
Charities welcomed the research but also urged caution.
Dr Sorrel Bickley, Research Communications Manager at the MS Society said: "This new study reports very encouraging findings, which add to a growing body of research into stem cell transplantation in MS. However, there are limitations to how we can interpret these results because there was no control group used, which means we can't be sure the results are robust.
"Momentum in this area of research is building rapidly and we're eagerly awaiting the results of larger, randomised trials and longer term follow up data.
"New treatments for MS are urgently needed, but as yet there are no stem cell therapies licensed for MS anywhere in the world. This means they aren't yet established as being both safe and effective. This type of stem cell therapy is very aggressive and does carry significant risks, so we would strongly urge caution in seeking this treatment outside of a properly regulated clinical trial."
The research was published in the Journal of the American Medical Association.
Source: The Daily Telegraph © Copyright of Telegraph Media Group Limited 2015 (02/03/15)
Stem cell treatment may cut new brain lesions in MS(12/02/15)
Multiple sclerosis patients who had autologous hematopoietic stem-cell transplantation had significantly fewer new lesions on MRI than those on mitoxantrone, Italian researchers have found.
In a randomized, controlled trial, CD34-positive hematopoietic cell transplant reduced the number of new T2 lesions by 79 per cent compared with mitoxantrone over a four-year study period, Giovanni Mancardi, MD, of the University of Genova in Italy, and colleagues reported in Neurology.
The therapy also reduced gadolinium-enhancing lesions and annualized relapse rate, but there was no difference in progression of disability, although the study was not powered to look at the latter finding, the researchers noted.
"More research is needed with larger numbers of patients who are randomized to receive either the stem-cell transplant or an approved therapy, but it's very exciting to see that this treatment may be so superior to a current treatment for people with severe MS that are not responding well to standard treatments," Mancardi said in a statement.
The ASTIMS study enrolled 21 patients from seven centers in Italy and Spain from 2004 to 2009 who had relapsing-remitting or secondary progressive MS. They were randomized to intensive immunosuppression followed by either mitoxantrone or autologous hematopoietic stem-cell transplantation every month for 6 months.
The intensive immunosuppression regimen involved mobilization with cyclophosphamide and filgrastim, conditioning with carmustine, cytosine arabinoside, etoposide, melphalan, and anti-thymocyte globulin.
The mean age at transplantation was 35.5 years, and the median Expanded Disability Status Scale (EDSS) score at baseline was 6.
ASTIMS was designed as a phase III study, but became a phase II trial with a primary laboratory endpoint -- the cumulative number of new T2 lesions 4 years after randomization -- "when it was clear that the number of enrolled patients was lower than expected," the researchers wrote.
Overall, Mancardi and colleagues found fewer T2 lesions in the stem-cell group than in the mitoxantrone group during follow-up at a median of 2.5 lesions versus a median of eight lesions.
This effect was evident in the first year and was sustained through four years of follow-up, they reported. It was also maintained in all sensitivity analyses. It also resulted in complete suppression of active inflammatory lesions as measured by gadolinium-enhancing lesions, with no stem-cell patients having new lesions compared with 56 per cent of those on mitoxantrone.
The annualized relapse rate was also lower for stem-cell patients. However, there was no significant difference in terms of progression of disability between groups, occurring in 48 per cent of the mitoxantrone group and 57 per cent of the stem-cell group, with no differences in EDSS changes at any point, the researchers said.
Mancardi and colleagues attributed this to the study being underpowered to look for this outcome.
In addition to this limitation, and the fact that the study was changed from phase III to phase II, it was also limited by its small number of cases and by a lack of data on quality of life and brain atrophy outcomes.
In an accompanying editorial, Paolo Muraro, MD, PhD, of Imperial College London, agreed that the lack of improvement in progression of disability was likely due to the study being underpowered.
Muraro also noted that mitoxantrone might not be the contemporary choice of comparator "having lost traction because of its cardiac toxicity and risk of lymphoma," although it was the most appropriate control treatment at the time the trial was started.
Given that stem-cell transplant isn't a licensed therapy for MS, more work is needed, Muraro said, noting that a phase III trial currently underway is likely to gain traction because the current study will "raise interest and catalyse activities to move forward with the new trial."
The study was supported by the Italian Multiple Sclerosis Foundation.
Mancardi disclosed relevant relationships with Bayer Schering, Biogen Idec, Genzyme, Merck Serono, Novartis, Sanofi, and Teva. Many co-authors disclosed multiple relevant relationships with industry including Biogen Idec, Novartis, Merk-Serono, Genzyme, Teva Pharmaceutical Industries, Genmab A/S, and Bayer Schering Pharma.
Muraro disclosed no relevant relationships with industry.
Source: MedPage Today © 2015 MedPage Today, LLC (12/02/15)
Stem cells reverse multiple sclerosis in small study(21/01/15)
A therapy that uses patients' own primitive blood cells may be able to reverse some of the effects of multiple sclerosis, a preliminary study suggests.
The findings, published Tuesday in the Journal of the American Medical Association, had experts cautiously optimistic.
But they also stressed that the study was small -- with around 150 patients -- and the benefits were limited to people who were in the earlier courses of multiple sclerosis (MS).
"This is certainly a positive development," said Bruce Bebo, the executive vice president of research for the National Multiple Sclerosis Society.
There are numerous so-called "disease-modifying" drugs available to treat MS -- a disease in which the immune system mistakenly attacks the protective sheath (called myelin) around fibres in the brain and spine, according to the society. Depending on where the damage is, symptoms include muscle weakness, numbness, vision problems and difficulty with balance and coordination.
But while those drugs can slow the progression of MS, they can't reverse disability, said Dr. Richard Burt, the lead researcher on the new study and chief of immunotherapy and autoimmune diseases at Northwestern University's Feinberg School of Medicine in Chicago.
His team tested a new approach: essentially, "rebooting" the immune system with patients' own blood-forming stem cells -- primitive cells that mature into immune-system fighters.
The researchers removed and stored stem cells from MS patients' blood, then used relatively low-dose chemotherapy drugs to -- as Burt described it -- "turn down" the patients' immune-system activity.
From there, the stem cells were infused back into patients' blood.
Just over 80 people were followed for two years after they had the procedure, according to the study. Half saw their score on a standard MS disability scale fall by one point or more, according to Burt's team. Of 36 patients who were followed for four years, nearly two-thirds saw that much of an improvement.
Bebo said a one-point change on that scale -- called the Expanded Disability Status Scale -- is meaningful. "It would definitely improve patients' quality of life," he noted.
What's more, of the patients followed for four years, 80 percent remained free of a symptom flare-up.
There are caveats, though. One is that the therapy was only effective for patients with relapsing-remitting MS -- where symptoms flare up, then improve or disappear for a period of time. It was not helpful for the 27 patients with secondary-progressive MS, or those who'd had any form of MS for more than 10 years. Secondary-progressive MS occurs when the disease progresses more steadily and people no longer go through waves of symptoms and recovery.
Between 250,000 and 350,000 Americans have MS, according to the National Institutes of Health (NIH). Most are initially diagnosed with the relapsing-remitting form. Eventually, relapsing-remitting MS transitions to the secondary-progressive form.
It makes sense that stem cell therapy would be effective only in the relapsing-remitting stage, according to Bebo. That's the phase where the immune system is actively attacking the myelin.
Burt agreed, noting that once people are in the secondary-progressive stage, the damage to nerves is done.
A big question is what will the long-range effects will be, according to an editorial published with the study.
MS usually arises between the ages of 20 and 40, according to the NIH. Since disabilities can take decades to develop, the ultimate benefits -- and risks -- of stem cell therapy remain unknown, writes Dr. Stephen Hauser, a neurologist at the University of California, San Francisco.
It's also unclear, Hauser writes, whether the therapy is really "resetting" the immune system.
Bebo agreed. "In this report," he said, "there's no data to show whether that's happening."
What's needed now, Bebo said, are controlled trials where patients are randomly assigned to receive stem cell therapy.
Burt agreed, and said that's what his team is doing: A clinical trial is underway at several medical centers, looking at patients with relapsing-remitting MS whose symptoms have failed to improve after at least six months on standard medications. They're being randomly assigned to either stem cell therapy or further drug therapy.
If stem cell therapy does prove effective, it's hard to say exactly how it will fit in with standard MS care, according to Bebo.
On one hand, the regimen is fairly intensive and expensive. "But in theory," Bebo said, "it would only have to be done once, and never again."
The disease-modifying drugs for MS -- such as beta interferons (Avonex, Rebif, Betaferon), glatirimer (Copaxone) and natalizumab (Tysabri) -- can cost thousands per month, according to the background information in the study.
Comparatively, stem cell therapy, at around $125,000, could prove very cost-effective, according to Burt.
For now, stem cell therapy is available only in clinical trials, or on a "compassionate use" basis for some patients who don't qualify for a trial, Burt said.
If it's eventually approved as an MS therapy, Burt said he foresees stem cells as a "second-line" therapy for patients who do not fare well on a disease-modifying drug.
Source: NEWSMAXHEALTH.COM © 2015 Newsmax Media, Inc (21/01/15)
Report of MS stem cell trial brings hope(05/01/15)
Three years after a small number of patients with multiple sclerosis (MS) were treated with high-dose immunosuppressive therapy (HDIT) and then transplanted with their own hematopoietic stem cells, most of the patients sustained remission of active relapsing-remitting MS (RRMS) and had improvements in neurological function, according to a study published online by JAMA Neurology.
MS is a degenerative disease and most patients with RRMS who received disease-modifying therapies experience breakthrough disease. Autologous (using a patient's own cells) hematopoietic cell transplant (HCT) has been studied in MS with the goal of removing disease-causing immune cells and resetting the immune system, according to the study background.
The Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) study examines the effectiveness of early intervention with HDIT/HCT for patients with RRMS and breakthrough disease. The article by Richard A. Nash, M.D., of the Colorado Blood Cancer Institute at Presbyterian/St. Luke's Medical Center, Denver, and coauthors reports on the safety, efficacy and sustainability of MS disease stabilisation though three years after the procedures. Patients were evaluated through five years.
Study results indicate that of the 24 patients who received HDIT/HCT, the overall rate of event-free survival was 78.4 percent at three years, which was defined as survival without death or disease from a loss of neurologic function, clinical relapse or new lesions observed on imaging. Progression-free survival and clinical relapse-free survival were 90.9 percent and 86.3 percent, respectively, at three years. The authors note that adverse events were consistent with the expected toxic effect of HDIT/HCT and that no acute treatment-related neurologic adverse events were seen. Improvements in neurologic disability, quality-of-life and functional scores also were noted.
"In the present study, HDIT/HCT induced remission of MS disease activity up to three years in most participants. It may therefore represent a potential therapeutic option for patients with MS in whom conventional immunotherapy fails, as well as for other severe immune-mediated diseases of the central nervous system. Most early toxic effects were hematologic and gastrointestinal and were expected and reversible. Longer follow-up is needed to determine the durability of the response," the authors conclude.
In a related editorial, M. Mateo Paz Soldán, M.D., Ph.D., of the University of Utah, Salt Lake City, and Brian G. Weinshenker, M.D., of the Mayo Clinic, Rochester, Minn., write: "This study and another phase 2 single-arm study leave little doubt that high-dose immunotherapy is able to substantially suppress inflammatory disease activity in patients with MS who have active disease in the short term. There is some evidence for long-term suppression of MS. Lessons have been learned about how treatment-related morbidity and mortality may be reduced. However, deaths have occurred, even in small studies, and aggressive regimens have resulted in lymphomas associated with Epstein-Barr virus."
"Nash et al show evidence of prolonged depletion of memory CD4+ cells, depletion of CD4+-dominant T-cell receptor clones and evidence of 'immune reset'; however, clinical or radiologic evidence of relapse trumps immunologic evidence of immune reset, and this study raises concern that those end points have not been adequately achieved. The jury is still out regarding the appropriateness and indication of HCT for MS," the authors conclude.
Source: Medical Xpress © Medical Xpress 2011-2015, Science X network (05/01/15)
Could mouse fat stem cells help study transplantation in Multiple Sclerosis(23/12/14)
Researchers in Spain have found that specific fat stem cells from mice could be excellent tools for studying transplantation of stem cells in autoimmune diseases, such as multiple sclerosis (MS). The work was published in the December 12th issue of the journal, Stem Cell Research & Therapy.
The type of cell is called a "mesenchymal stem cell" or MSC for short. They are found in adults in the bone marrow, but can also be found in other regions like the umbilical cord or regular blood in the circulatory system, as well as the fallopian tubes and lungs.
Scientists are avidly studying these cells for the possible treatment of autoimmune diseases like MS because of their ability to change into almost any cell type. They eventually would like to see whether these cells can be used to treat disease in humans. According to the study authors, "The ultimate goal in MSCs research is to treat human patients at the clinic with their own MSCs, since autologous transplantation provides two main theoretical advantages: a minimisation of the risk of transmission of infectious diseases and an increased efficiency in the absence of rejection by the patient's immune system."
If people could use their own MSCs to treat disease, rejection of the cells due to immune responses would be brought to a minimum.
With this idea in mind, researchers decided to test whether cells taken from the fat of mice (adipose tissue) would have the qualities needed for MSCs. This was not just any mouse, but a specific type of mouse called the SJL/JCrl mouse strain, which has been studied in research on retinal degeneration and also in genetically-modified mice (transgenic). This animal was compared to the more commonly-studied C57BL/6 mouse strain.
The scientists, led by Carmen Marin-Bañasco of the Instituto de Biomedicina de Málaga, examined how the stem cells from the SJL/JCrl mouse grow, how quickly they develop, what shapes they take on, and different markers on the surface of the cells that could tell them what type of cell they turn into. In the most critical experiment, the scientists tried transplanting mice with the stem cells that had a mouse version of relapsing-remitting multiple sclerosis, known as experimental autoimmune encephalomielitis (RR-EAE).
Based on their experiments, these particular fat cells had the shape, growth rate, and other cell characteristics that are classic for a potential MSC. Transplanting the fat stem cells helped the mice with the experimental form of MS, by reducing markers of inflammation in the spinal cord and brain and making the nervous system tissue take on a less-diseased appearance.
The authors concluded that the fat cells in this type of mouse might be useful for testing transplantation in animals, before researchers conduct similar studies in humans. Similar types of cells would then need to be studied in greater detail in humans, but could eventually be useful for "their application as promising therapeutic tools in experimental medicine for autologous transplantations." Fat cells in humans might eventually be good for transplantation from the same person that provided the fat, to treat or possibly even cure their disease.
Source: Multiple Sclerosis News Today © BioNews-tx.com 2014 (23/12/14)
Placental cells appear safe for patients with MS(30/09/14)
Early evidence suggests value treatment effectiveness.
Patients with Multiple Sclerosis (MS) were able to safely tolerate treatment with cells cultured from human placental tissue, according to a study published today in the journal Multiple Sclerosis and Related Disorders. The study, which is the first of its kind, was conducted by researchers at Mount Sinai, Celgene Cellular Therapeutics subsidiary of Celgene Corporation and collaborators at several other institutions.
While designed to determine safety of the treatment, early signals in the data also suggested that a preparation of cultured cells called PDA-001 may repair damaged nerve tissues in patients with MS. PDA-001 cells resemble "mesenchymal," stromal stem cells found in many tissues of the body. Since the cells are expanded in cell cultures, one donor is able to supply enough cells for many patients.
"This is the first time placenta-derived cells have been tested as a possible therapy for multiple sclerosis," said Fred Lublin, MD, Director of the Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Professor of Neurology at Icahn School of Medicine at Mount Sinai and the lead investigator of the study. "The next step will be to study larger numbers of MS patients to assess efficacy of the cells, but we could be looking at a new frontier in treatment for the disease."
MS is a chronic autoimmune disease in which the body's immune system mounts recurring assaults on the myelin--the fatty, protective coating around nerve fibers in the central nervous system. This causes nerves to malfunction and can lead to paralysis and blindness. The disease usually begins as an episodic disorder called relapsing-remitting MS (RRMS), and for many sufferers, evolves into a chronic condition with worsening disability called secondary progressive MS (SPMS).
The new safety study was conducted on 16 MS patients (10 with RRMS and six with SPMS) between the ages of 18 and 65. Six patients were given a high dose of PDA-001, another six were given a lower dose, and four patients were given placebo. Any time the immune system is altered, say by an experimental treatment, there is always a risk for MS to worsen, noted Dr. Lublin. All subjects were given monthly brain scans over a six-month period to ensure they did not acquire any new or enlarging brain lesions, which would indicate a worsening of MS activity. No subjects showed any paradoxical worsening on MRI and after one year, the majority had stable or improved levels of disability.
"We're hoping to learn more about how placental stromal cells contribute to myelin repair," said Dr. Lublin. "We suspect they either convert to a myelin making cell, or they enhance the environment of the area where the damage is to allow for natural repair. Our long-term goal is to develop strategies to facilitate repair of the damaged nervous system."
Collaborators in the study included the Swedish Neuroscience Institute in Seattle, WA, MultiCare Health System-Neuroscience Center of Washington, London Health Sciences Centre at University Hospital in London, the Clinical Neuroscience Research Unit at the University of Minnesota, the University of Colorado Denver, The Ottawa Hospital Multiple Sclerosis Clinic, and the MS Comprehensive Care Center at SUNY.
Dr. Fred Lublin has received research support and financial compensation as an advisory board member from Celgene, the study's sponsor.
Source: EurekaAlert! ©2014 by AAAS, the science society (30/09/14)
Early trial of stem cells for multiple sclerosis shows promise(22/09/14)
An early clinical trial testing the use of a patient's own stem cells to treat, or even reverse, multiple sclerosis has shown some positive results, Cleveland Clinic researchers reported this week.
The Phase 1 trial, unique in the United States, tested the safety and feasibility of treating MS patients with a dose of their own adult mesenchymal stem cells, or MSCs. Found in the bone marrow, MSCs are being tested in more than 150 clinical trials in the U.S. and abroad as a way to treat a variety of other conditions such as osteoarthritis, diabetes, emphysema and stroke.
Dr. Jeffrey Cohen, director of the Clinic's Mellen Center for Multiple Sclerosis Treatment and Research, presented the findings at the MSBoston2014 convention, which opened Wednesday in Boston.
Multiple sclerosis is an autoimmune disease in which the immune system attacks the myelin sheaths that surround and protect nerve cells. When myelin is damaged, the nerve cells are exposed and unable to do their job, which is sending signals to the brain and back. This results in the loss of motor skills, coordination and cognitive abilities.
Cohen worked with a team at University Hospitals Seidman Cancer Center and Case Western Reserve University on the trial, which completed when the last patient finished the protocol in January. A total of 24 patients with relapsing forms of MS received injections of their own MSCs, which were harvested at UH, carefully cultivated in a special laboratory at CWRU and then injected intravenously back into the patient at the Clinic.
"We really encountered no practical issues and there really were no safety issues," said Cohen, noting the concern that experimental MS treatments can sometimes trigger relapse.
While the study was not designed to measure for benefit — it did not have a comparison group and involved a small group of patients — Cohen said the researchers were encouraged by what they saw.
"We didn't see any dramatic changes in anybody, but looking at the results as a whole there really were some encouraging trends, which is really as much as you hope to see in this kind of study," he said.
Cohen and his team plan a follow-up, larger Phase 2 trial that would further examine the safety of the technique but also more directly look for benefit to patients. Because of the initial positive safety results, patients in future trials won't have to come to the Clinic for visits quite as frequently for monitoring, he said.
"We had very frequent visits, lots of safety testing, so it was very difficult for someone who was not right in the area to participate," he said. "We'll be able to tone down the safety monitoring a bit so it will be a much more feasible study for trial participants to participate in."
The local team also plans a trial that will track the MSCs after they're injected, which remains an unanswered question within the stem cell field — where the cells go, where they migrate to within the body, and whether they survive. The team hopes to label the cells and track them by magnetic resonance imaging.
Both studies should be underway by next year.
Source: Cleveland.com © Plain Dealer Publishing Co. and Northeast Ohio Media Group (22/09/14)
Could reprogrammed cells fight 'untreatable' diseases?(28/08/14)
Jeanne Loring and her Scripps Research Institute colleagues transplanted a set of cells into the spinal cords of mice that had lost use of their hind limbs to multiple sclerosis. As the experimentalists expected, within a week, the mice rejected the cells. But after another week, the mice began to walk.
"We thought that they wouldn't do anything," says Loring, who directs the Center for Regenerative Medicine at Scripps. But as her lab has since shown numerous times, and published in Stem Cell Reports, something that these particular so-called "neural precursor cells" do before the immune system kicks them out seems to make the mouse better.
The cells Loring's team used are derived from induced pluripotent stem cells, which are mature cells, such as skin cells, that have been coaxed with a combination of chemicals to return to an earlier stage of development.
Induced pluripotent cells, also known as iPS cells, pose a number of opportunities for medicine. For instance, Loring is using iPS cells from Parkinson's disease and multiple sclerosis patients to reconstitute cell types that may be damaged in people with those conditions. She is also using them to test how certain drugs or treatments may affect damaged cells in people with conditions such as autism spectrum disorders.
Loring says no viable long-term treatments exist for the diseases her team has been working on, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis, "That's where the need is," she says.
The neural precursor cells that Loring has been using in the mice with MS are young cells that haven't quite gotten to the point of being nerves yet. Only certain types of these cells have such a dramatic Lazarus-like effect on the affected mice, but Loring's team can readily identify them based on DNA analysis.
Even so, they're not yet ready to treat human MS patients with the approach, she says. First, the researchers want to identify what the cells produce—a protein, perhaps, or a set of proteins—that allows the mice to walk.
For other diseases, however, researchers are closer to being ready to transplant working versions of reprogrammed cells into sick people.
For instance, Loring is exploring whether it's possible to reprogram skin cells from patients with Parkinson's disease so they turn into iPS cells and then into working dopamine neurons, which are the cells affected in the disease.
It seems to work in animals: Loring's lab has transformed skin cells from eight human Parkinson's disease patients into iPS cells and transplanted them as neurons into animal models.
A local Southern California Parkinson's disease association has funded the research so far. Now Loring and colleagues are seeking additional funds to move through regulatory approval and toward the clinic.
Meanwhile, iPS cells separately suggest a way to test how disease-affected cells may or may not respond to treatment in diseases like autism, by in effect creating "dummy" cells on which drugs could be tested.
After making iPS cells from the cells of fragile X syndrome patients, a genetic condition that often co-occurs with some forms of autism, Loring's lab turned them into cortical neurons—cells that she suspects don't develop as they should in people with the disorder.
Indeed, the cortical neurons her lab grew from those iPS cells looked different than other cortical neurons and suffered delayed development. These neurons, she explains, could be used to test different molecules and compounds to see whether drugs could treat cells affected by autism.
This sort of approach, in which so-called "derived cells" are used for drug screening, Loring said, is the likely way that iPS cells will first be used in medicine, especially as more and more people have their genomes analyzed. Treatment with reprogrammed iPS cells will take longer to develop.
Loring says she hopes soon to be able to set up simple assays "that will allow us to find out what sort of drugs will work for people with particular genotypes." That could offer a significant boost to drug development. iPS cells are an important new opportunity to attack diseases that otherwise have vexed researchers and doctors for decades.
Source: Techonomy © Forbes 2014 (28/08/14)
Scientists one step closer to cell therapy for multiple sclerosis patients(25/07/14)
Scientists at The New York Stem Cell Foundation (NYSCF) Research Institute are one step closer to creating a viable cell replacement therapy for multiple sclerosis from a patient's own cells.
For the first time, NYSCF scientists generated induced pluripotent stem (iPS) cells lines from skin samples of patients with primary progressive multiple sclerosis and further, they developed an accelerated protocol to induce these stem cells into becoming oligodendrocytes, the myelin-forming cells of the central nervous system implicated in multiple sclerosis and many other diseases.
Existing protocols for producing oligodendrocytes had taken almost half a year to produce, limiting the ability of researchers to conduct their research. This study has cut that time approximately in half, making the ability to utilize these cells in research much more feasible.
Stem cell lines and oligodendrocytes allow researchers to "turn back the clock" and observe how multiple sclerosis develops and progresses, potentially revealing the onset of the disease at a cellular level long before any symptoms are displayed. The improved protocol for deriving oligodendrocyte cells will also provide a platform for disease modeling, drug screening, and for replacing the damaged cells in the brain with healthy cells generated using this method.
"We are so close to finding new treatments and even cures for MS. The enhanced ability to derive the cells implicated in the disease will undoubtedly accelerate research for MS and many other diseases," said Susan L. Solomon, NYSCF Chief Executive Officer.
"We believe that this protocol will help the MS field and the larger scientific community to better understand human oligodendrocyte biology and the process of myelination. This is the first step towards very exciting studies: the ability to generate human oligodendrocytes in large amounts will serve as an unprecedented tool for developing remyelinating strategies and the study of patient-specific cells may shed light on intrinsic pathogenic mechanisms that lead to progressive MS". said Dr. Valentina Fossati, NYSCF – Helmsley Investigator and senior author on the paper.
In multiple sclerosis, the protective covering of axons, called myelin, becomes damaged and lost. In this study, the scientists not only improved the protocol for making the myelin-forming cells but they showed that the oligodendrocytes derived from the skin of primary progressive patients are functional, and therefore able to form their own myelin when put into a mouse model. This is an initial step towards developing future autologous cell transplantation therapies in multiple sclerosis patients.
This important advance opens up critical new avenues of research to study multiple sclerosis and other diseases. Oligodendrocytes are implicated in many different disorders, therefore this research not only moves multiple sclerosis research forward, it allows NYSCF and other scientists the ability to study all demyelinating and central nervous system disorders.
"Oligodendrocytes are increasingly recognized as having an absolutely essential role in the function of the normal nervous system, as well as in the setting of neurodegenerative diseases,such as multiple sclerosis. The new work from the NYSCF Research Institute will help to improve our understanding of these important cells. In addition, being able to generate large numbers of patient-specific oligodendrocytes will support both cell transplantation therapeutics for demyelinating diseases and the identification of new classes of drugs to treat such disorders," said Dr. Lee Rubin, NYSCF Scientific Advisor and Director of Translational Medicine at the Harvard Stem Cell Institute.
Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system, distinguished by recurrent episodes of demyelination and the consequent neurological symptoms. Primary progressive multiple sclerosis is the most severe form of multiple sclerosis, characterized by a steady neurological decline from the onset of the disease. Currently, there are no effective treatments or cures for primary progressive multiple sclerosis and treatments relies merely on symptom management.
NYSCF stem cell researcher Valentina Fossati, PhD, is the senior author and NYSCF researcher Panagiotis Douvaras, PhD, is the first author of this study.
Key collaborators on this research included Dr. Saud Sadiq and the Tisch Multiple Sclerosis Research Center of New York where patients were recruited, Dr. Fraser Sim of the State University of New York at Buffalo for the in vivo studies, and Dr. James Goldman of Columbia University Medical Center.
The New York Stem Cell Foundation research was supported by a NYSCF – Helmsley Early Career Investigator Award, The New York Stem Cell Foundation, and The Leona M. and Harry B. Helmsley Charitable Trust. The in vivo studies were supported by the Empire State Stem Cell Fund through New York State Department of Health.
Source: EurekaAlert Copyright ©2014 by AAAS, the science society (25/07/14)
'Master switch' for myelination in human brain stem cells is identified(01/07/14)
Scientists at the University at Buffalo have identified the single transcription factor or "master switch" that initiates the critical myelination process in the brain. The research will be published online in Proceedings of the National Academy of Sciences (PNAS) on June 30.
The identification of this factor, SOX10, in human brain cells, brings researchers closer to the goal of treating multiple sclerosis (MS) by transplanting into patients the brain cells that make myelin.
"Now that we have identified SOX10 as an initiator of myelination, we can work on developing a viral or pharmaceutical approach to inducing it in MS patients," says Fraser Sim, PhD, senior author on the paper and assistant professor in the UB Department of Pharmacology and Toxicology in the School of Medicine and Biomedical Sciences.
"If we could create a small molecule drug that would switch on SOX10, that would be therapeutically important," he adds.
Stem cell therapy is seen as having dramatic potential for treating MS, but there are key obstacles, especially the length of time it takes for progenitor cells to turn into oligodendrocytes, the brain's myelin-making cells.
Using currently available methods, Sim explains, it can take as long as a year to generate a sufficient number of human oligodendrocyte cells to treat a single MS patient. That's partly because there are so many steps: the skin or blood cell must be turned into induced pluripotent stem cells, which can differentiate into any other type of cell and from which neural progenitor cells can be produced. Those progenitor cells then must undergo differentiation to oligodendrocyte progenitors that are capable of ultimately producing the oligodendrocytes.
"Ideally, we'd like to get directly to oligodendrocyte progenitors," says Sim. "The new results are a stepping stone to the overall goal of being able to take a patient's skin cells or blood cells and create from them oligodendrocyte progenitors," he says.
Using fetal (not embryonic) brain stem cells, the UB researchers searched for transcription factors that are absent in neural progenitor cells and switched on in oligodendrocyte progenitor cells.
While neural progenitor cells are capable of producing myelin, they do so very poorly and can cause undesirable outcomes in patients, so the only candidate for transplantation is the oligodendrocyte progenitor.
"The ideal cell to transplant is the oligodendrocyte progenitor cell," Sim says. "The question was, could we use one of these transcription factors to turn the neural progenitor cell into an oligodendrocyte progenitor cell?"
To find out, they looked at different characteristics, such as mRNA expression, protein and whole gene expression and functional studies.
"We narrowed it down to a short list of 10 transcription factors that were made exclusively by oligodendrocyte progenitor cells," says Sim. "Among all 10 factors that we studied, only SOX10 was able to make the switch from neural progenitor to oligodendrocyte progenitor cell," says Sim.
In addition, the UB researchers found that SOX10 could expedite the transformation from oligodendrocyte progenitor cell to differentiation as an oligodendrocyte, the myelin-producing cell and the ultimate treatment goal for MS.
"SOX10 facilitates both steps," says Sim.
That's tantalizing, he says, because one of the biggest problems with MS is that cells get stuck in the step between the oligodendrocyte progenitor cell and the oligodendrocyte. "In MS, first the immune system attacks the brain, but the brain is unable to repair itself effectively," explains Sim. "If we could boost the regeneration step by facilitating formation of oligodendrocytes from progenitor cells, then we might be able to keep patients in the relapsing remitting stage of MS, a far less burdensome stage of disease than the later, progressive stage."
Sim is also an investigator with other scientists at UB and the University of Rochester on the $12.1 million New York State Stem Cell Science award led by SUNY Upstate Medical Center. The research will test the safety and effectiveness of implanting stem cells that can reproduce myelin into the central nervous system of MS patients.
Source: Medical Xpress © Medical Xpress 2011-2014 (01/07/14)
Future embryonic stem cell treatment promise for multiple sclerosis(19/06/14)
Scientists in the University of Connecticut's Technology Incubation Program have identified a novel approach to treating multiple sclerosis (MS) using human embryonic stem cells, offering a promising new therapy for more than 2.3 million people suffering from the debilitating disease.
The researchers demonstrated that the embryonic stem cell therapy significantly reduced MS disease severity in animal models, and offered better treatment results than stem cells derived from human adult bone marrow.
The study was led by ImStem Biotechnology Inc. of Farmington, Conn., in conjunction with UConn Health Professor Joel Pachter, Assistant Professor Stephen Crocker, and Advanced Cell Technology (ACT) Inc. of Massachusetts. ImStem was founded in 2012 by UConn doctors Xiaofang Wang and Ren-He Xu, along with Yale University doctor Xinghua Pan and investor Michael Men.
"The cutting-edge work by ImStem, our first spinoff company, demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside," says Professor Marc Lalande, director of the UConn's Stem Cell Institute.
The research was supported by a $1.13 million group grant from the state of Connecticut's Stem Cell Research Program that was awarded to ImStem and Professor Pachter's lab.
"Connecticut's investment in stem cells, especially human embryonic stem cells, continues to position our state as a leader in biomedical research," says Gov. Dannel P. Malloy. "This new study moves us one step closer to a stem cell-based clinical product that could improve people's lives."
"The cutting-edge work by ImStem ... demonstrates the success of Connecticut's Stem Cell and Regenerative Medicine funding program in moving stem cells from bench to bedside. - Marc Lalande"
The researchers compared eight lines of adult bone marrow stem cells to four lines of human embryonic stem cells. All of the bone marrow-related stem cells expressed high levels of a protein molecule called a cytokine that stimulates autoimmunity and can worsen the disease. All of the human embryonic stem cell-related lines expressed little of the inflammatory cytokine.
Another advantage of human embryonic stem cells is that they can be propagated indefinitely in lab cultures and provide an unlimited source of high quality mesenchymal stem cells - the kind of stem cell needed for treatment of MS, the researchers say. This ability to reliably grow high quality mesenchymal stem cells from embryonic stem cells represents an advantage over adult bone marrow stem cells, which must be obtained from a limited supply of healthy donors and are of more variable quality.
"Groundbreaking research like this furthering opportunities for technology ventures demonstrates how the University acts as an economic engine for the state and regional economy," says Jeff Seemann, UConn's vice president for research.
The findings also offer potential therapy for other autoimmune diseases such as inflammatory bowel disease, rheumatoid arthritis, and type-1 diabetes, according to Xu, a corresponding author on the study and one of the few scientists in the world to have generated new human embryonic stem cell lines.
There is no cure for MS, a chronic neuroinflammatory disease in which the body's immune system eats away at the protective sheath called myelin that covers the nerves. Damage to myelin interferes with communication between the brain, spinal cord, and other areas of the body. Current MS treatments only offer pain relief, and slow the progression of the disease by suppressing inflammation.
"The beauty of this new type of mesenchymal stem cells is their remarkable higher efficacy in the MS model," says Wang, chief technology officer of ImStem.
Source: MNT © MediLexicon International Ltd 2004-2014 (19/06/14)/p>
Walking mice kick off new area of MS stem cell research(12/05/14)
Mice severely disabled by a multiple sclerosis (MS)-like condition could walk less than two weeks following treatment with human stem cells. The finding, which uncovers new avenues for treating MS, will be published online in the journal Stem Cell Reports.
When scientists transplanted human stem cells into MS mice, they predicted the cells would be rejected, much like rejection of an organ transplant.
Expecting no benefit to the mice, they were surprised when the experiment yielded spectacular results.
"My postdoctoral fellow Dr. Lu Chen came to me and said, 'The mice are walking.' I didn't believe her," said co-senior author, Tom Lane, a professor of pathology at the University of Utah, who began the work at University of California, Irvine.
Within just 10 to 14 days, the mice regained motor skills. Six months later, they still showed no signs of slowing down.
"This result opens up a whole new area of research for us," said co-senior author Jeanne Loring, co-senior author and professor at The Scripps Research Institute in La Jolla, Calif.
More than 2.5 million people worldwide have MS, a disease where the immune system attacks myelin, an insulation layer surrounding nerve fibres. The resulting damage inhibits nerve impulses, producing symptoms that include difficulty walking, impaired vision, fatigue and pain.
The MS mice treated with human stem cells experience a reversal of symptoms. Immune attacks are blunted, and damaged myelin is repaired, explaining their dramatic recovery. The discovery could help patients with latter, or progressive, stages of the disease, for whom there are no treatments.
Counterintuitively, the researchers' original prediction that the mice would reject the stem cells, came true. There are no signs of the cells after one week. In that short window, they send chemical signals that instruct the mouse's own cells to repair the damage caused by MS. This realisation could be important for therapy development.
"Rather than having to engraft stem cells into a patient, which can be challenging, we might be able to put those chemical signals into a drug that can be used to deliver the therapy much more easily," said Lane.
With clinical trials as the long-term goal, the next steps are to assess durability and safety of the stem cell therapy in mice.
"I would love to see something that could promote repair and ease the burden that patients with MS have," said Lane.
Source: University of Utah Health Sciences (12/05/14)
Autologous haematopoietic stem cell transplantation for aggressive MS: the Swedish experience(28/04/14)
BACKGROUND: Autologous haematopoietic stem cell transplantation (HSCT) is a viable option for treatment of aggressive multiple sclerosis (MS). No randomised controlled trial has been performed, and thus, experiences from systematic and sustained follow-up of treated patients constitute important information about safety and efficacy. In this observational study, we describe the characteristics and outcome of the Swedish patients treated with HSCT for MS.
METHODS: Neurologists from the major hospitals in Sweden filled out a follow-up form with prospectively collected data. Fifty-two patients were identified in total; 48 were included in the study and evaluated for safety and side effects; 41 patients had at least 1 year of follow-up and were further analysed for clinical and radiological outcome. In this cohort, 34 patients (83%) had relapsing-remitting MS, and mean follow-up time was 47 months.
RESULTS: At 5 years, relapse-free survival was 87%; MRI event-free survival 85%; expanded disability status scale (EDSS) score progression-free survival 77%; and disease-free survival (no relapses, no new MRI lesions and no EDSS progression) 68%. Presence of gadolinium-enhancing lesions prior to HSCT was associated with a favourable outcome (disease-free survival 79% vs 46%, p=0.028). There was no mortality. The most common long-term side effects were herpes zoster reactivation (15%) and thyroid disease (8.4%).
CONCLUSIONS: HSCT is a very effective treatment of inflammatory active MS and can be performed with a high degree of safety at experienced centres.
Burman J, Iacobaeus E, Svenningsson A, Lycke J, Gunnarsson M, Nilsson P, Vrethem M, Fredrikson S, Martin C, Sandstedt A, Uggla B, Lenhoff S, Johansson JE, Isaksson C, Hägglund H, Carlson K, Fagius J.
Sources: J Neurol Neurosurg Psychiatry. 2014 Feb 19. doi: 10.1136/jnnp-2013-307207 & Pubmed PMID: 24554104 (28/04/14)
Multiple sclerosis umbilical cord stem cell therapy clinical trial approved(03/04/14)
Translational Biosciences, a subsidiary of Medistem Panama, has received the green light for a phase I/II clinical trial using human umbilical cord-derived mesenchymal stem cells (UC-MSC) for multiple sclerosis from the Comité Nacional de Bioética de la Investigación (CNEI) Institutional Review Board (IRB) in Panama.
According to the US National Multiple Sclerosis Society, in Multiple Sclerosis (MS), an abnormal immune-mediated T cell response attacks the myelin coating around nerve fibers in the central nervous system, as well as the nerve fibers themselves. This causes nerve impulses to slow or even halt, thus producing symptoms of MS that include fatigue; bladder and bowel problems; vision problems; and difficulty walking. The Cleveland Clinic reports that MS affects more than 350,000 people in the United States and 2.5 million worldwide.
Mesenchymal stem cells harvested from donated human umbilical cords after normal, healthy births possess anti-inflammatory and immune modulatory properties that may relieve MS symptoms. Because these cells are immune privileged, the recipient's immune system does not reject them. These properties make UC-MSC interesting candidates for the treatment of multiple sclerosis and other autoimmune disorders.
Each patient will receive seven intravenous injections of UC-MSC over the course of 10 days. They will be assessed at 3 months and 12 months primarily for safety and secondarily for indications of efficacy.
The stem cell technology being utilised in this trial was developed by Neil Riordan, PhD, founder of Medistem Panama. The stem cells will be harvested and processed at Medistem Panama's 8000 sq. ft. ISO-9001 certified laboratory in the prestigious City of Knowledge. They will be administered at the Stem Cell Institute in Panama City, Panama.
From his research laboratory in Dallas, Texas, Dr. Riordan commented, "Umbilical cord tissue provides an abundant, non-controversial supply of immune modulating mesenchymal stem cells. Preclinical and clinical research has demonstrated the anti-inflammatory and immune modulating effects of these cells. We look forward to the safety and efficacy data that will be generated by this clinical trial; the first in the western hemisphere testing the effects of umbilical cord mesenchymal stem cells on patients with multiple sclerosis."
The Principle Investigator is Jorge Paz-Rodriguez, MD. Dr. Paz-Rodriguez also serves as the Medical Director at the Stem Cell Institute. For detailed information about this clinical trial visit http://www.clinicaltrials.gov.
Source: PR Web ©Copyright 1997-2014, Vocus PRW Holdings, LLC (03/04/14)
Stem cells from muscle may repair nerve damage due to MS - study(20/03/14)
Stem cells derived from human muscle tissue were able to repair nerve damage and restore function in an animal model of sciatic nerve injury, according to researchers at the University of Pittsburgh School of Medicine. The findings, published online today in the Journal of Clinical Investigation, suggest that cell therapy of certain nerve diseases, such as multiple sclerosis, might one day be feasible.
To date, treatments for damage to peripheral nerves, which are the nerves outside the brain and spinal cord, have not been very successful, often leaving patients with impaired muscle control and sensation, pain and decreased function, said senior author Johnny Huard, Ph.D., professor of orthopaedic surgery, and Henry J. Mankin Chair in Orthopaedic Surgery Research, Pitt School of Medicine, and deputy director for cellular therapy, McGowan Institute for Regenerative Medicine.
"This study indicates that placing adult, human muscle-derived stem cells at the site of peripheral nerve injury can help heal the lesion," Dr. Huard said. "The stem cells were able to make non-neuronal support cells to promote regeneration of the damaged nerve fiber."
The researchers, led by Dr. Huard and Mitra Lavasani, Ph.D., first author and assistant professor of orthopaedic surgery, Pitt School of Medicine, cultured human muscle-derived stem/progenitor cells in a growth medium suitable for nerve cells. They found that, with prompting from specific nerve-growth factors, the stem cells could differentiate into neurons and glial support cells, including Schwann cells that form the myelin sheath around the axons of neurons to improve conduction of nerve impulses.
In mouse studies, the researchers injected human muscle-derived stem/progenitor cells into a quarter-inch defect they surgically created in the right sciatic nerve, which controls right leg movement. Six weeks later, the nerve had fully regenerated in stem-cell treated mice, while the untreated group had limited nerve regrowth and functionality. Twelve weeks later, treated mice were able to keep their treated and untreated legs balanced at the same level while being held vertically by their tails. When the treated mice ran through a special maze, analyses of their paw prints showed eventual restoration of gait. Treated and untreated mice experienced muscle atrophy, or loss, after nerve injury, but only the stem cell-treated animals had regained normal muscle mass by 72 weeks post-surgery.
"Even 12 weeks after the injury, the regenerated sciatic nerve looked and behaved like a normal nerve," Dr. Lavasani said. "This approach has great potential for not only acute nerve injury, but also conditions of chronic damage, such as diabetic neuropathy and multiple sclerosis."
Drs. Huard and Lavasani and the team are now trying to understand how the human muscle-derived stem/progenitor cells triggered injury repair, as well as developing delivery systems, such as gels, that could hold the cells in place at larger injury sites.
Journal Reference:
Mitra Lavasani, Seth D. Thompson, Jonathan B. Pollett, Arvydas Usas, Aiping Lu, Donna B. Stolz, Katherine A. Clark, Bin Sun, Bruno Péault, Johnny Huard. Human muscle–derived stem/progenitor cells promote functional murine peripheral nerve regeneration. Journal of Clinical Investigation, 2014; DOI: 10.1172/JCI44071
Source: Science Daily Copyright 2014 by ScienceDaily, LLC (20/03/14)


text:
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Cloche Encounter of the Cute Kind
When I saw this hat, it was like nothing I'd ever seen before! It had a retro 20's, flapper-like silhouette, and was cream in color with a distinctive black, floral, satiny embellishment on the right side. When I got close enough to look at it, I also noticed it was 100% wool, and all too adorable! It has since left my sight, but I look forward to the next sighting of this cloche, most likely on a really hip, retro and trendy online website, and then, hopefully, I'll have the chance to capture one of my own! -Julie, Fashion Writer
- 100% wool
- 25 inches in radius, 6.5 inches deep
- Spot clean
- Imported

subset: commoncrawl


text:
Millennium Park
Invisible Exhibition
This is a very unique interactive 1½-hour `tour' of a half-different settings (bus, crossing the road, taking a bus) in the total...
Mammut Bowling Club
Bowling is enjoying something of a resurgence here and alleys are rolling out across town, especially in shopping malls. One of the best...
House of the Future Exhibition
The House of the Future Exhibition in Millennium Park hosts some unusual shows for kids.
Auguszt Cukrászda
Tucked away behind the Fény utca market and Mammut shopping mall complex, this is the original Auguszt (there are two newer branches in...
This odd place is a hang-out for teens, who have added a layer of their own graffiti to the Communist memorabilia and kitsch – a joke...
II Kis Rókus utca 16-20 · interesting places nearby
Millennium Park information
Millennium Park is an attractive landscaped complex comprising fountains, ponds, little bridges, a theatre, a playground and a gallery containing the Invisible Exhibition , a unique interactive 1½-hour 'tour' of a half-dozen settings (crossing the road, taking a bus) in total darkness, led by a blind or partially sighted person. The idea is to help participants understand what life is like without the one sense that provides us with the most information.
Also here is the Millennium Theatre . You can also enter the park from Fény utca 20-22 and Lövőház utca 37.


text:
Patients and Staff Move Out of Princess Royal Hospital and into New Cancer Centre
A new pounds70m cancer centre has opened for patients at Castle Hill Hospital in Cottingham.
The opening of the pounds70m oncology and haematology centre came after patients and staff relocated from the Princess Royal Hospital in east Hull over the weekend.
Health services have been provided at the Princess Royal site in Saltshouse Road for more than 80 years.
All that remains now is a dermatology outpatients service, which is scheduled to move out later this year.
Ward sister Clare Norris has worked at Princess Royal since 1987.
She said: "I've got very mixed emotions because I've got many happy memories of working here. It's sad to be leaving, but very exciting at the same time to be moving into such a wonderful new facility."
Cervical cancer sufferer Dawn Gatenby, 35, from Goole, was among 37 patents being ferried across the city to Cottingham in a fleet of ambulances.
Before leaving, she said: "I am looking forward to it because the staff are coming with us.
"Everyone says it's like being in a five-star hotel, but a building is only as good as its staff and they have been brilliant."
The new facility certainly has the feel of a luxury hotel, with open-plan seating areas, cutting-edge technology, high- specification architecture and landscaped courtyards.
Inside, consultant haematologist Dr Russell Patmore confessed to shedding a few tears when the first patients started arriving
"This is the culmination of 10 years' planning. I think it's been a great achievement for everyone concerned."
(c) 2008 Hull Daily Mail (UK). Provided by ProQuest LLC. All rights Reserved.


text:
- Shopping Bag ( 0 items )
Publishers WeeklyMultimedia journalist Stasi (Boomer Babes: A Woman's Guide to the New Middle Ages) tries her hand at a religious thriller with mixed results. New York City reporter Ali Russo is covering the U.N. tribunal of Demiel ben Yusef, "a known terrorist who was believed by most of the reasonable people on the planet, as well as the worldwide coalition of governments who'd hunted him and finally captured him, to be the one responsible for terrorist bombings around the world." On the other hand, some believe Yusef is "the second Son of God." When fate allows the heavily guarded Yusef to plant a kiss on a stunned Russo's lips outside the General Assembly building, she not only becomes the object of media frenzy but soon finds herself a murder suspect and the target of an international hunt. Unwillingly cast in the role of "the Chosen One," Russo remains more pawn than queen in Stasi's clumsy chess game. Still, the author deserves credit for an imaginative if far-fetched premise. Agent: Liza Flessig, Liza Royce Literary Agency.
(c) Copyright PWxyz, LLC. All rights reserved.


text:
Mon-Fri: 7am-1am EST / Sat-Sun: 7am-11pm EST
ApplianceMaytag Dryer
Level of DifficultyReally easy
Time to do repair15 - 30 mins
Age of Appliance5 - 10 years
1 out of 1 people found this instruction helpful
Disconnected power....lifted the top of the dryer to gain access to parts requiring replacement... Unsrcewed two screws 1/4 inch nutdriver....disconnected the two wires...connected the wires to the new part and attached screws...Removed 1 screw from heat element and raised element to get to heat sensor...sensor pops out removed wires and popped new sensor in...replaced wires closed top lid reconnected power source and started dryer
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Part Number: PS2162282
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Articles Tagged 'EGM Employment'
EGM Employment: News Editor
By EGM Staff
Posted on March 29, 2013 AT 08:00am
Posted on March 29, 2013 AT 08:00am
Are you passionate about tracking down the latest gaming news and reporting it in an informative, entertaining way for readers? Are you not satisfied simply rehashing press releases but tracking down facts and breaking stories of your own? If so, then EGM might be for you! READ MORE
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Until Dawn Announced For August 25th With New Trailer, Pre-Order Bonus Scene, And Screenshots
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text:
Your POV
Masky left, he said he had to take care of something. I stayed home and went into my room. I went on my computer and lodged into Facebook. There I saw a bunch of post from kids at school. They were all talking about what happened today and they shared how they felt about my ex cheating on me.
'Dudes this guy came to my school and totally owned (Ex's name)! It was awesome!'
'Ladies beware. (Ex's name) is a dog! He will cheat on you.'
'I thought (Ex's name) was a cool guy. Until I found out he cheated on his girl!'
'Some guy came and schooled (Ex's name) I posted it on my YouTube so you could see for your self.'
'I feel really bad for (Name). No wonder she seemed so depressed lately'
'Don't worry (Name) I know what it's like to be cheated on. There are other guys in the world that are loyal to their girls. Like me ^^'
'(Ex's name) your a bad person and you should feel bad!'
'Hang in there (Name)'
'(Ex's name) cheated on (Name). Is he a jerk or what?'
'I heard (Ex's name) cheated in his girlfriend with (Enemy's name) and she's a fucking slut! I heard she slept with the whole basketball team.'
'(Ex's name) you are a liar and a cheater and you don't deserve a girlfriend! And (Enemy's name) your a whore!'
I couldn't help but smile at the post. Know everyone knows what he did to me. I hear my cell phone ring and see that I got a text. I look at it and see it was from (Ex's name) saying 'Can we talk?' I text back 'NO!'. For the next few minutes he calls and text me trying to get me to talk to him. But I'm not falling for it. I hear the door bell ring. Thinking it was Masky I walk out my room, go down stairs and open the door. Only to see that it was my ex. I slam the door in his face yelling "Go away!" "(Name) please I just wanna talk." he begged. "Leave before I have you arrested for trespassing!" "Go ahead, cause I'm not leaving until we talk." Defeated I open the door. "What do you want?" "Look (Name) I know your mad, and you have every right to be. I did something horrible. But please believe that I really am sorry. Let me make it up to you. Give me another chance." he pleaded.
"No. Its like he said. You had your chance and you blew it. You decided to push me off for the girl you know I hate. Even if I hadn't met someone else I still wouldn't take you back because I know for a fact you would just do it again. I gave you my trust, I gave you my heart and you shredded them like paper! I thought you might have actually been the one for me! I thought I loved you but obviously I was wrong! Your nothing but a liar and user! And to think I blamed myself for what you did! I thought you cheated because I wasn't pretty enough, that I wasn't good enough! I thought you cared about me but you obviously don't give a damn about how I care! And not once did you try to apologize for what you did before today! Your only apologizing because everyone knows what you did and you just don't want to deal with the humiliation! Your not sorry because you feel bad! YOUR SORRY BECAUSE YOU GOT CAUGHT!! YOUR SORRY BECAUSE EVERYONE KNOWS THE KIND OF PERSON YOU ARE!!! DO YOU EVEN HAVE ANY IDEA OF THE PAIN YOU PUT ME THROUGH?!?! ALL THE NIGHTS I CRIED MY SELF TO SLEEP WONDERING WHY YOU DID THIS TO ME?!?! I HATE YOU (Ex's name)!!! I HATE YOU MORE THAN ANYTHING AND I WISH YOU WOULD JUST DROP DEAD!!!"
I slammed the door again only harder this time. "(Name) please I.....I'm sorry." I stormed up the stairs and into my room. I grabbed the pillow off my bed and scream into it as loud as I could. After a few minutes of sobbing I went out like a light.
'My poor, poor (Name). Your don't deserve all this suffering you've gone through.' I walk over to the bed and neal down so I'm face to face with her. I take off my cap to help get a better look. I kiss her cheek and leave her to sleep. If (Name) is ever going to be mine, I need to eliminate the completion. I hope Hoodie doesn't mind working alone.
A Masked Romance Masky X Reader Pt. 4 by Mizomim
©2013-2015 Mizomim
I personally think that the song
Your not sorry, by Taylor Swift
Fits this perfectly.
Your not sorry, by Taylor Swift
Fits this perfectly.
Whose dis gonna be....? I'm gonna continue reading to find out.
hmmm a cap . . . . the only pastas i can think of that have caps are glitchy red, strangled red, and lost silver so i'm gonna just go and keep reading and find out :3
I think it might be ticci toby
i thing it might be jeff
is it weirde that im reading this and listening to party music? XDDDD DEH PARTY FEELS MIZED WITH IDK FEELSSSS
Damn, I dont read Pokepasta D: I dont know the diffrence on em'! Whats Strangled red? Glitchy red? Whaa? Huhidontunderstandanything >.<
Im reading this...while listening to the song 'Listen to your Heart' by DHT...
and somehow I feel emotional for some reason...
and somehow I feel emotional for some reason...
IS he a Jerk...OR NAH
OMG OMG OMG OMGO OMG OMG OMG OMG OMG why you always do this? you killing me right now D:
h-Hoodie? NO! Your Masky's best bro can't do this to him!!!! (cries in a corner)
Please not Strangled red.. i love him Dx
What's the difference between strangled red and glitchy red ?
Besides the obvious .
Besides the obvious .
*realisation hits* OMFG POKÉPASTA'S WHICH ONE IS IT?!
*realisation hits* OMFG POKÉPASTA'S WHICH ONE IS IT?!
It's either Glitchy Red or Strangled Red....and i think it is Strangled Red.
I think the only creepypasta that has a cap is that Pokemon guy one (I hope I'm right)
There actually two pokemon guys with caps
I can think at least four people who it could be. Time to go find out.
Ben know it the word that points it out is cap
Is it ticci Toby?


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About Schools in Terre Hill, PA
Contact a Coldwell Banker® real estate agent to learn more about the schools and school districts in Terre Hill, PA.FIND AN AGENT
Terre Hill, Pennsylvania is located in Lancaster County. Nearby cities and towns include Fivepointville, Blue Ball, Goodville, Bowmansville, East Earl, New Holland, Reamstown, Churchtown, Swartzville, Adamstown, Farmersville, Alleghenyville, Denver, Stevens, Ephrata, Gouglersville, Akron, Morgantown, Reinholds, Honey Brook, Leola, New Morgan, Intercourse, Schoeneck, Brownstown, Mohnton, Pennwyn, Rothsville, Gordonville, Montrose Manor, Clay, Flying Hills, Shillington, Bird-in-Hand, Ronks, Lincoln Park, Paradise, Soudersburg, Witmer, Grill, Sinking Spring, Elverson, Smoketown, West Wyomissing, Kenhorst, Gap, Springmont, Wernersville, West Lawn, Hopeland, Whitfield, Wyomissing, Gibraltar, Brickerville, West Reading, Colony Park, Lititz, Spring Ridge, Robesonia, Lorane, Reading, Strasburg, Christiana, Reiffton, Mount Penn, Birdsboro, Greenfields, Georgetown, St. Lawrence, Atglen, Baumstown, Lampeter, Pennside, Lancaster, Parkesburg, Newmanstown, Womelsdorf, Schaefferstown, Jacksonwald, Pomeroy, East Petersburg, Hyde Park, Stony Creek Mills, Westwood, Muhlenberg Park, Riverview Park, Willow Street, Fox Chase, Penryn, Coatesville, Laureldale, Richland, Refton, South Temple, Stouchsburg, Caln, South Coatesville, Manheim, Amity Gardens, Douglassville, Temple, Modena, Quarryville, Bernville, Millersville, Thorndale, Alsace Manor, Landisville, Cochranville, Myerstown, Cornwall, Leesport, Salunga, Stowe, Eagleview, Dauberville, Kirkwood, Oley, Conestoga, Downingtown, New Schaefferstown, South Pottstown, Avon, Blandon, Mountville, Quentin, Kenilworth, Lebanon South, Hebron, Mount Aetna, Pottstown, Mohrsville, Centerport, Lionville, Mount Gretna Heights, Walnuttown, Mount Gretna, Rehrersburg, Halfway House, Lebanon, Timber Hills, Fleetwood, Exton, Sand Hill, Shoemakersville, Strausstown, Mount Joy, Pleasant Hill, Pottsgrove, Shartlesville, Washington Boro, and Boyertown. Terre Hill is a rural community with a population of 1,328. The median household income is $49,765. In Terre Hill, 63% of residents are married, and families with children reside in 29% of the households. Half the population of Terre Hill commutes 16 minutes or less to work, with 39% of residents holding white collar jobs and 61% residents holding blue collar jobs. The median age of homes in Terre Hill, PA is 59 years, with 69% of those homes owned, 27% rented, and 4% not occupied. In the previous year, 14 Terre Hill properties were sold. The median sale price of a home in Terre Hill in the previous year was $170,514.
Contact a Coldwell Banker® real estate agent to learn more about the schools and school districts in Terre Hill, PA.FIND AN AGENT
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Community information and market data Powered by Onboard Informatics. Copyright ©2015 Onboard Informatics. Information is deemed reliable but not guaranteed.
This information is provided for general informational purposes only and should not be relied on in making any home-buying decisions. School information does not guarantee enrollment. Contact a local real estate professional or the school district(s) for current information on schools. This information is not intended for use in determining a person's eligibility to attend a school or to use or benefit from other city, town or local services.


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I am creating a website using Ruby on Rails 3. I have been working on this project for 2 months and everything was working fine. Suddenly I get the following error after I added the gem 'ckeditor', '3.4.2.pre' to my gemfile. I followed the ckeditor tutorial here: http://hafizbadrie.wordpress.com/2011/07/31/rails-3-and-ckeditor/ and everything worked fine but since then whenever I run any command like rails server or bundle install on my console I get the following error:
WARNING: Invalid .gemspec format in '/usr/lib/ruby/gems/1.8/specifications/arel-0.3.3.gemspec'
/usr/local/lib/site_ruby/1.8/rubygems.rb:777:in `report_activate_error': Could not find RubyGem rails (>= 0) (Gem::LoadError)
from /usr/local/lib/site_ruby/1.8/rubygems.rb:211:in `activate'
from /usr/local/lib/site_ruby/1.8/rubygems.rb:1056:in `gem'
from /usr/bin/rails:18
I searched on Google and got a solution saying run gem install bundler but that did not solve my error. Because of this error I am not able to proceed further since not a single command is running.
How can i solve this error? thanks in advance...


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A brief Overview
Humans began nearly a million years ago. They were little more than animals then. But soon showed themselves to be the top of the food chain. But the gods and goddesses couldn't let the humans grow to powerful. All life forms must have a predator, including the humans. So they created the vampires.
Vampires were faster, stronger, and more beautiful than the humans. They drank human blood to survive. But in many ways humans and vampires were alike. Vampires, while more beautiful, looked very much like humans. Enough so that one could pass as human for a short period of time. Vampires and humans could have children. Vampires loved, loss, and hated like humans.
But all the similarities couldn't change the fact the vampires weren't human. If a vampire stayed around humans too long, the humans would start to notice that he/she wasn't one of them. Vampires didn't just look and move differently than humans. They also thought differently. No emotion they had was stronger than their bloodlust and because of that vampires were cunning, ruthless, and, at times, heartless. They were constantly hungry and never satisfied with what they had.
That hunger for more only increased when the humans began to use magic. Since human bodies weren't forged with magic they were able to act as conduit for the magic around them. Allowing them to use the magic to heal the wounded, protect the tribe, and to help keep the land fertile for farming.
The vampires were jealous that the weak and inferior humans could gain such power and tried to attain it for themselves. But they couldn't because their bodies already had so much magic in them that they couldn't allow any more into them. In a rage against the humans for their newfound power the vampires slaughtered many tribes. For a time it seemed as if they would continue to murder the humans until none were left. But then the magic users banded together and struck back. With their combined might they drove the vampires back from the tribes and into hiding. For a thousand years vampires and humans fought, neither gaining ground on the other. Many said the war would never end until one of them was dead, but those people hadn't counted on the arrival of another race.
A shunned human spell caster created the shapeshifters when he messed up a spell. He intended to kill the wolf, but instead merged with it. When he realized what he did he went to the village where he grew up to punish his mother for banishing him. As he made his way to his mother's tent he killed and bit as many people as he could. But he hadn't counted on his mother being prepared for him. Once he finally approached her, she killed him. While doing it left a black mark on her soul, she knew it was the correct thing to do.
She went about to heal the injured, but found that they couldn't be heal with magic. So, she bandaged them up as best she could and hoped that they would survive. The next morning they were all healed. While some took that to mean the gods were pleased with them, she wasn't so sure. She knew the only way those wounds could have healed so quickly was with magic. But no one listened to her and after a month of celebrating the miraculous feet the full moon rose in the sky. The men, women, and children that had been bit all screamed in agony as their bones snapped and reformed. The painful transformation finally ended after a few minutes and where humans once stood, wolves stood in their place.
The mother went to the vampires to get help, but they laughed at her and told her to get lost. So she walked and walked and walked until her feet would no longer hold her. Then she layed down and waited for death.
Minutes after she left the shapeshifters attacked the vampire camp. They slaughtered every last one they could find and then as the sun rose they underwent the horrendous transformation back into humans.
When the rest of the vampire population heard of the massacre they banded together and prepared to strike back. But the humans stopped them. The witches explained what happened and this time the vampires listened. After hearing the story they agreed to help the humans drive the wolves away. Thus, ending the war between the witches and vampires.
They succeeded in driving the shifters away and with peace among them once again, the humans and vampires lived happily for the next ten thousand years. Then the shifters came back.


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George Dyson:
George Dyson: 電腦的誕生
歷史學家George Dyson講述現代電腦誕生時的故事——從16世紀電腦的起源到一些早期電腦工程師的搞笑筆記本。
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Chicago Cubs' Most Heartbreaking Prospect Busts of Recent Years
Chicago Cubs' Latest Flops
Recently MLB.com updated their top 100 MLB prospects list and three of the Chicago Cubs biggest "stars in the making", shortstop Javier Baez and outfielders Albert Almora and Jorge Soler, made the cut at 16th, 39th, and 42nd, respectively. The list, which is produced by MLB.com's draft and prospect expert Jonathon Mayo, is always fun to look at for several hours on end, but will undoubtedly become a source of disappointment at one point or another. Attempting to predict which prospects will develop into serviceable, everyday players at the highest level by analyzing scouting reports is unthinkable for me. Unfortunately, it's easier to scrutinize prospect rankings than it is to put in the countless hours of research to create them. The fact is, players that are considered top prospects in the early stages of their professional careers can end up "flopping."
Remember Kevin Orie? Brooks Kieschnick? What about Luis Montanez? At one time all three were highly regarded as promising MLB prospects within the Cubs organization but never lived up to the hype. The probability of Baez, Almora, and Soler all developing into dangerous players at the big league level is, to the dismay of all Cubs fans, pretty remote. Luckily, those same fans have experienced this heartbreak before. Let's take a look back at some of the biggest and most heartbreaking Cubs prospect flops of recent memory.
Corey Patterson OF
Corey Patterson was regarded as a five-tool player with tremendous upside. In 2002, the athletic, 22-year-old outfielder got his first chance at a full season with the Cubs after zipping right through the Minor League system. He hit just .253 and struck out 142 times. In 2003, Patterson busted out and was on track for a 30-30 season before getting injured half way through the year and missing the rest of the season. After bouncing back with 26 home runs and 32 stolen bases in 2004, Patterson has failed to produce at a consistent level ever since and has played for five different organizations in the last five years.
Jake Fox C/OF/PH
Jake Fox was a beast when he was coming up through the Minor League system. The outfielder/catcher had the sort of raw power that could have allowed him to put up huge offensive numbers. Fox produced home run totals of 21, 24, and 31 in three Minor League seasons from 2006 to 2008. In 2009, Fox was absolutely terrorizing Triple-A pitching and was hitting a laughable .409 with 17 bombs through 45 games before getting the call to the Majors. In 82 games with the Cubs that season, Fox put together a respectable rookie campaign by hitting .259 with 11 home runs and 44 RBIs, but that was the most production anyone would ever see from him again. The Cubs traded Fox to the Oakland Athletics and since then he's bounced around a bit. Now 30-years-old with just 20 career big league home runs to his credit, Fox was last seen somewhere in the Philadelphia Phillies organization.
Mark Prior RHP
I didn't want to begin the list with Mark Prior but I didn't want to end with him either, just to give readers a better chance of forgetting this one. He was going to be the ace of the Cubs staff for many years. He had the perfect mechanics, strength, command, work ethic, and competitive drive to win multiple Cy Young awards, but he hasn't pitched in the MLB since 2006 when he was just 25 years old. After being drafted as the 2nd overall pick of the 2001 amateur draft out of USC, Prior needed just nine Minor League appearances before making his MLB debut in 2002. He finished his first full season in 2003 with an 18-6 record and a 2.43 ERA to finish third in the Cy Young award voting at the tender age of 22. Unfortunately, that year would end up being the highlight of his career as injuries would plague him every year thereafter. Prior has been attempting a comeback in recent years, and last year he pitched 19 games for the Boston Red Sox Triple-A affiliate. Now let's move on because it's just too painful to think about what could have been for the former phenom.
Felix Pie OF
In 2007, the 22-year-old Felix Pie was crushing Triple-A pitching to a clip of .362 with nine home runs in 55 games when he was given a shot at big league pitching. He hit just .215 in 87 games with the Cubs the rest of the way. In 2008, the young Dominican's struggles continued before a recall to the minors. Later that winter, Pie was dealt to the Baltimore Orioles for a couple of young pitching prospects. In Baltimore, he was given opportunities to play, but his career .298 on-base percentageisn't even close to what was expected of him.
Angel Guzman RHP
Angel Guzman was considered a very dangerous pitching prospect at one time in his professional career. His Minor League numbers are a good indication of just how much potential Guzman had as he posted records of 9-1 and 11-4 in his first two professional seasons in Single-A ball. He was promoted to the Chicago Cubs in 2006 at 24 years old, but he struggled to establish his command as a starting pitcher, going 0-7 in his first three stints in the Major Leagues. Guzman was converted to a relief pitcher and in 2009 put together a commendable year out of the Cubs bullpen, appearing in 55 games with a 2.95 ERA. However, Guzman was sidelined for the entire 2010 season with an injury and has yet to fully recover. In 2012, Guzman pitched in the Los Angeles Dodgers organization, and now a 30-year-old, will try to make a comeback.
Honorable Mentions
Hee Seop Choi 1B
Hee Seop Choi was supposed to be the "big bopper" in the middle of the Cubs lineup for many years and scouts regarded his defense just as highly. The big 6'5" 235-pound first baseman clubbed 26 home runs with Triple-A Iowa in 2002, before being called up to the big leagues where he .180 in 50 at bats with two just home runs. In 2003, Choi hit just .218 in 202 at bats with eight home runs, while striking out in a third of his plate appearances. Nothing ever fully developed for Choi in Chicago, nor with stints with the Florida Marlins and Los Angeles Dodgers. However, Choi did make a name for himself as the first Korean-born position player to play in the Major Leagues. I'll never forget his head-on collision with Kerry Wood in a game that left Choi knocked out on the ground for several minutes.
Dave Kelton OF
Dave Kelton wasn't regarded quite as highly as a top prospect as others on this list, but with just 22 career plate appearances in the MLB after an impressive Minor League career, it's hard for me to forego his inclusion. With Triple-A Iowa in 2003, Kelton hit 19 home runs to add to his previous Minor League totals of 13, 18, 12, 20, and 16. However, he could never quite make the turn from dangerous Minor League hitter to serviceable big league talent, and by the time he was 26 he decided to call it quits.
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Volkswagen AG switched on its largest photo-voltaic installation worldwide as Europe's biggest carmaker builds on its U.S. auto factory's recognition by an environmental group for sustainable operations.
You are here
SEIA is the solar energy industry's go-to source for the latest coverage on solar power, including U.S. and international policy, research and polls, business and financing trends, and more. Our staff strives to support the media covering solar energy issues and guide our members on effective media outreach with clear statements, background materials, news and multimedia resources.
SEIA is committed to informing policymakers, the media, and the American public about the benefits of solar energy for today's communities, our economy, and our country.
Learn more from our statements and industry news below.
Solar Power Installations Hit Record in Mass.
Massachusetts recorded its largest number of new solar power installations in 2012, as hundreds of homeowners and large institutions and businesses, such as schools and big box stores, took advantage of government-backed incentives for renewable resources.
Time for Private Purchases of Renewable Power
Five years ago, North Carolina became the first state in the Southeast to set a renewable energy and efficiency standard. The 12.5 percent by 2021 standard is a great goal, and we should keep raising the bar.
FERC's Small Generator Interconnection Procedures (SGIP)
FERC issued a notice of proposed rulemaking to update its SGIP. Among several changes, it proposes to modify the Supplemental Review process; making it similar to the California Rule 21 process - a 100% of minimum load screen along with two additional technical screens that evaluate a generators' impact on safety, reliability and power quality. FERC will host an additional workshop and provide an opportunity for written comments on the proposed changes before finalizing the rule.
OHIO PUC Proposes Interconnection Revisions
On January 16, 2013, the Ohio Public Utility Commission staff issued proposed revisions to that state's interconnection procedures for comment. A supplemental review process with a 100% of minimum load penetration screen and two additional technical screens are among the changes proposed. Comments are due later in January with reply comments in February. Read the full text.
San Diego Could Be Getting More Solar Power
Solar backers and at least one member of the California Public Utilities Commission think there could be a lot more solar panels on roof tops around the state. The CPUC's Mike Peevey is asking regulators to change how utilities count the customers who sell power back into the grid, in a practice called "net metering."
Goldman Sets $40 Bln Clean Energy Investment Plan
Goldman Sachs Group Inc plans to channel investments totaling $40 billion over the next decade into renewable energy projects, an area the investment bank called one of the biggest profit opportunities since its economists got excited about emerging markets in 2001.
Shift by U.S. Muddles Solar Imports Case
Renewable energy companies around the world are awaiting a decision Thursday by the U.S. Commerce Department on whether to impose anti-dumping tariffs on solar panels imported from China, as a little-noticed policy shift by the department last year has made the outcome of the case unusually hard to predict
Tracy Solar Build Gets White House Go Ahead
A solar power plant that the city of Tracy hopes to build has cleared a major hurdle that's taken 14 years to accomplish.
CPUC on the Verge of Major Decision About Solar's Net Metering
A fight over the future of net energy metering (NEM) in California is expected to be decided in a May 24 California Public Utilities Commission (CPUC) decision on the arcane question of how to define the NEM cap. It has become a battleground over NEM for investor-owned utilities (IOUs) and solar advocates.


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NEW YORK ( TheStreet) -- Wells Fargo was the winner among the nation's banks on Thursday, with shares rising over 2% to close at $37.42.
The broad indices ended with slight gains, as news of economic stimulus in Japan overshadowed rising U.S. unemployment claims.
The Nikkei 225 in Japan rose by 2.2% after the Bank of Japan announced aggressive monetary easing, increasing its monthly government bond purchases to about 7 trillion yen from roughly 4 trillion yen a month.
The Labor Department reported that initial unemployment claims in the U.S. increased by 28,000 to a four-month high of 385,000 in the week ended March 30 from 357,000 in the prior week. Economists polled by Thomson Reuters were expecting net jobless claims to decline to 350,000.The four-week moving average for first-time unemployment claims increased by 11,250 to 354,520. The KBW Bank Index (I:BKX) rose 1% to close at 55.16, with all but two of the 24 index components showing gains.
Big Four Cheap to Forward EarningsFirst-quarter earnings season for banks will be kicked off by JPMorgan Chase (JPM - Get Report) and Wells Fargo (WFC - Get Report) before the market opens on April 12. As the broad recovery for bank stocks continues, the "big four" U.S. banks -- which also include Bank of America (BAC - Get Report) and Citigroup (C - Get Report) -- continue to have low relative stock valuations. For an outline on what to expect from the largest financial players next week, please see TheStreet's earnings preview for the big four. Jefferies analyst Ken Usdin said in a report on Thursday that, on average, regional banks trade for 1.5 times tangible book value and 12.6 times 2014 earnings estimates. The big four provide a stark comparison to those numbers.
- JPMorgan's shares closed at $47.49 Thursday, trading for 1.3 times tangible book value, according to Thomson Reuters, and for 8.2 times the consensus 2014 earnings estimate of $5.81 a share. Analysts expect the company to report first-quarter earnings of $1.39 a share next Friday. The consensus EPS estimate for all of 2013 is $5.48.
- Wells Fargo's shares trade for 1.7 times tangible book value and for 9.6 times the consensus 2014 EPS estimate of $3.89. When the company reports its first-quarter results next Friday, analysts expect EPS of 88 cents. The consensus EPS estimate for all of 2013 is $3.65.
- Bank of America's stock closed at $11.90 Thursday, trading for 0.9 times tangible book value and for 9.1 times the consensus 2014 EPS estimate of $1.31. The company is scheduled to announce its first-quarter results on April 17, with a consensus EPS estimate of $23 cents. The consensus EPS estimate for all of 2013 is 98 cents.
- Citigroup's shares closed at $42.77 Thursday, trading for 0.8 times tangible book value and for 8.2 times the consensus 2014 EPS estimate of $5.22. Analysts on average expect Citi to post first-quarter EPS of $1.18 when the company reports on April 15. The consensus EPS estimate for all of 2013 is $4.61.
Wells Fargo
With "limited near-term catalysts for positive EPS revisions," Usdin wrote that his research team remains "biased toward a barbell strategy," with 12 picks among regional bank stocks. Wells Fargo is among the banks rated "buy" by Usdin, with a price target of $42.00. The analyst estimates the company will report first-quarter earnings of 87 cents a share, declining from 91 cents in the fourth quarter, and 88 cents in the first quarter of 2012. "We expect WFC's eleven quarter streak of Q-Q EPS growth to come to an end as softer mortgage banking and seasonality are simply too much to overcome," Usdin wrote. Jefferies expects Wells Fargo's mortgage revenue to decline by $200 million from the fourth quarter, from lower gain-on-sale margins as the market has pushed up long-term rates. On a positive note, Usdin has "confidence in WFC's ability to ratchet back expenses," and he expects a relatively small narrowing of the company's net interest margin from the fourth quarter. -- Written by Philip van Doorn in Jupiter, Fla. >Contact by Email. Follow @PhilipvanDoorn


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Acorn Academy Cornwall is an Alternative Provision (AP) Multi Academy Trust (MAT) that comprises of 6 regional AP Academies, The Community and Hospital Education Service (CHES) a medical AP Academy.
We provide support to enable pupils to reintegrate into mainstream or special schools; or in the last four terms of compulsory education, integration into the world of work or further education.
Visit our About Us page for more information.