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Cholesterol-lowering drugs and the risk of hemorrhagic stroke
Contact: Angela Babb
American Academy of Neurology
ST. PAUL, Minn. – People taking cholesterol-lowering drugs such as atorvastatin after a stroke may be at an increased risk of hemorrhagic stroke, or bleeding in the brain, a risk not found in patients taking statins who have never had a stroke. But researchers caution the risk must be balanced against the much larger overall benefit of the statin in reducing the total risk of a second stroke and other cardiovascular events when making treatment decisions. The research is published in the December 12, 2007, online issue of Neurology®, the medical journal of the American Academy of Neurology.
For the study, researchers conducted a secondary analysis of the results of the Stroke Prevention with Aggressive Reduction in Cholesterol Levels (SPARCL) clinical trial. The trial enrolled 4,731 people who were within one to six months of having had a stroke or transient ischemic attack, or mini-stroke, and with no history of heart disease. Half of the participants received atorvastatin and half received a placebo. The participants were then followed for an average of four and a half years.
Overall, treatment was associated with a 16-percent reduction in total stroke, the study's primary endpoint, as well as significant reductions in coronary heart events. However, secondary analysis found that the overall reduction in stroke included an increase in the risk of brain hemorrhage. Of those people randomized to atorvastatin, the study found 2.3 percent experienced a hemorrhagic stroke during the study compared to 1.4 percent of those taking placebo. The study also found there was a 21-percent reduction in ischemic stroke, a more common type of stroke involving a block in the blood supply to the brain, among people taking atorvastatin.
Other factors were also found to increase the risk of brain hemorrhage. For example, those who had experienced a hemorrhagic stroke prior to the study were more than five times as likely to suffer a second stroke of this kind. Men were also nearly twice as likely as women to suffer a hemorrhagic stroke. People with severe high blood pressure at their last doctor's visit prior to the hemorrhagic stroke had over six times the risk of those with normal blood pressure.
"Although treatment of patients with a stroke or transient ischemic attack was clearly associated with an overall reduction in a second stroke, hemorrhagic stroke was more frequent in people treated with atorvastatin, in those with a prior hemorrhagic stroke, in men and in those with uncontrolled hypertension," according to study author Larry B. Goldstein, MD, with Duke University Medical Center in Durham, North Carolina, and Fellow of the American Academy of Neurology. "This risk of hemorrhagic stroke also increased with age."
"Treatment with atorvastatin did not disproportionately increase the frequency of brain hemorrhage associated with these other factors. The risk of hemorrhage in patients who have had a transient ischemic attack or stroke must be balanced against the benefits of cholesterol-lowering drugs in reducing the overall risk of a second stroke, as well as other cardiovascular events," said Goldstein.
The SPARCL trial was funded by Pfizer, the maker of atorvastatin.
The American Academy of Neurology, an association of more than 20,000 neurologists and neuroscience professionals, is dedicated to improving patient care through education and research. A neurologist is a doctor with specialized training in diagnosing, treating and managing disorders of the brain and nervous system such as stroke, Alzheimer's disease, epilepsy, Parkinson disease, and multiple sclerosis.
For more information about the American Academy of Neurology, visit http://www.aan.com.
by Jeanne Hambleton © 2007
NFA Leader Against Pain – Advocate
Maybe I should mention that you just might need some kleenex tissues before you start this story but please read it anyway, if only in the spirit of Goodwill to All Children. The men are big enough to look after themselves.
As folks in the UK were getting ready this morning to do some Christmas shopping an email arrived on my desktop with a warning, which said, "This email needs to circulate forever."
How could I pass up this invitation to inquire within? The email also stated, "This is a real eye opener. A real tear jerker No prerequisites (commitments). Simply, because everyone should be reminded."
This was sent to me by a lady from Montevideo, Uruguay called Marta. Where the pictures, shown in the email, were taken, it does not say, but I am sure it conveys a worldwide message, especially within the African continent.
Picture 1. shows European students sat at computers working, with the caption, "Does studying annoy you?"
Picture 2. reveals children, possibly from Africa, without shoes, sat on a bench and drawing their lessons in the dirt with their fingers. The caption says, " Not them!"
Picture 3. is a happy family picture of a father with his daughter enjoying a beef burger roll with the words, "Hate veggies?"
Picture 4. is a picture of a long line of native mothers and starved children, clothed, in rags and waiting in line with a bowl for some food handouts. This caption says, "They starve from hunger!"
Picture 5. reveals the back view of a jolly obese child having fun, with a caption which reads, "On a diet?"
Picture 6. gives a close-up of a painfully thin starved child with a tape measure around the child's matchstick thin arm. The caption referring to diet says, "They die from it!" Or the lack of any kind of diet.
Picture 7. shows a baby being cuddled by a parent revealing the lovely cuddly cheeks of a child's bottom. This reads, "Does your parent's care tire you?"
Picture 8. shows a sibling cuddling a child with the last bone in the baby's spine clearly visible as she rests in sister's arms for comfort. This caption tells us these children have no parents to grow tired of. "They don't have any!"
Picture 9. reveals youngsters sat at a games console and states, "Bored with the same game?"
Picture 10. Shows a young unclothed child playing in the dirt with a bit of stick, next to the human skull of someone who had probably died from starvation. The caption reads, "They have no option!"
Picture 11. shows a smart new trainer with a caption which reads, "Someone got you Adidas instead of Nike?"
Picture 12. pictures the feet of a child with half of a plastic bottle cut to make the sole of a pair of sandals. The picture clearly reveals the screw top of the plastic bottle on the footwear, which is tied onto the foot with rag. This caption states, "They only have one brand?" Maybe it is cola?????
Picture 13. is of a sweet little girl in clean pyjamas snuggled up in her cosy bed. This caption reads, "Aren't you thankful for a bed to sleep in?"
Picture 14. The final contrast picture shows a child laying in the dirt, half covered with a piece of old rag, trying to sleep, with a caption that reads, "They'd wish not to wake up!"
The closing slide asks, "Are you still complaining? Observe around you and be thankful for all that you have in this transitory lifetime…. We are fortunate to have much more than what we need to be content. Let us try not to feed this endless cycle of consumerism and immortality in which this 'modern and advanced' society forgets and ignores the other two thirds of our brothers and sisters. Send this information without any obligation or expectation in receiving good luck. Don't keep it! Send it and it won't be in vain. Let us complain less and give more!"
I imagine you feel as I do. I work hard for my dollar and I do not believe in sharing my hard earned cash with large charities who have magnificent offices, managing directors, hundreds of paid staff and devote just a fraction of their donations to their 'good' works. You can call me the woman with the long pockets if you like, but I want to know my money is going where it will doing some good and helping those would really need it. How to be confident about that I am not sure? In true Scorpion fashion I hate to be misled or deceived.
Quite how we can help these starving children is the burning question. I have had masses of appeals for all sorts of charities drop on my doormat in recent weeks. At least these ends up in the local hospice waste paper recycling skip and help them a little along with our papers and magazines. I looked on the Internet at our UK BBC Children in Need but could not see children in a similar situation.
The UK Save the Children organisation has produced a Christmas shopping catalogue, on line, so should you decide to buy Christmas gifts from them you are indirectly donating while shopping, just how much remains to be seen! Perhaps this might be more acceptable – buying and giving at the same time. It is easy to look at this site to see the work they are doing and possibly shop with them. Every Christmas I seem to receive more and more cards printed by charities and sent by to me by friends.
However I should mention that if you telephone their UK number – 0844 557 5425 – instead of ordering on line, it could cost you 40p a minute as you give your details and make your mind up. Some of that money will be going to the charity.
Our doctors' surgery is using this 0844 prefix number and getting a rake off which is a bit vexing considering how much our GPs are reported to be earning – but that is another story.
No – I am not a sales rep for any charity – just a concerned parent. No, this is not a commercial for children's charities – it is a wake up call.
The American Save the Children website also appears to have a programme for under privileged children in developing countries, who are suffering from hunger and poverty. It seems you can also purchase festive gifts from them indirectly helping the cause.
What you decide to do is between you and your conscience. I would however like to leave you with these thoughts.
These pictures and words certainly do bring you down to earth especially when you consider the wastage by governments the world over. I am just sorry I could not reproduce the pictures but I am sure you know the kind of scenes I mean – you must have seen them on TV from time to time. Send me your email address with the request for these pictures if you would like them forwarding.
Just consider the money all of the worldwide governments squander… it is time someone added the total figure and gave us some home truths.
These starving children, if they live, may be our next generation – our future leaders. Do you think if they survive they could be future terrorists? I am sure they will have a grudge against the world – surely they will feel the world owes them a living. This is all very sad and really makes you think. Whatever happened to the innocence of childhood?
Just imagine what we spend on consumerism not to mention what we will spend on our own children this Christmas 2007. I wonder what our children would think if we put these pictures under the Christmas tree on Dec.25 instead of a new bike, a new game toy and all the other things children of our modern world expect to receive from their parents aka Father Christmas?
What would it be like if children all over the world went without just one toy from their festive gifts in aid of the starving and poverty stricken children. It would take a lot of organizing to gather in that money and it is a huge task but it could be done – all it needs is a good website supported by reliable well known people…. even if it took until Easter to collect the money – the children would still be starving.
Where are you Bob Geldorf? Can you help us with this? Does someone know his email address? My mind is boggling at the power of the people…… How about Skinny Kids for a campaign title – that rather sums it up!
Just a thought – maybe if that £5 we would be spending on a nonsense stocking gift for someone who has everything, was replaced with a warm note telling them Christmas is for children – starving children in particular – and they would be receiving his gift money with a tax gift aid. Sorry but this has been sent to starving "Skinny Kids" who have nothing.
I would hope we would get a really warm hug for this initiative. This friend really did not need an air freshener toy for his car or a key ring. If we did not get a big hug that receiver is a Christmas Meanie…. Take it from me. We will cross him off our Christmas list in future – so there.
Sorry to be a party pooper – but someone has to do it. I will make up for it and send you some happier stories in the near future.
Take care. Jeanne.
A pioneering study opens roads for tailor-made antidepressants
In spite that the causes of depression have not still been fully identified, scientists acknowledge that genetic and environmental factors play a common role in the onset of this disorder. One of the environmental risk factors more often related to depression is exposure to threatening life events. On the other side, from a genetic point of view, the serotonin transporter gene, with a crucial role in communication between neurons, could predispose to depression.
An international group of scientists, headed by professors Jorge Cervilla Ballesteros and Blanca Gutiérrez Martínez, from the department of Legal Medicine, Toxicology and Psychiatry of the University of Granada, has recently published in the prestigious journal Molecular Psychiatry the pioneering study PREDICT-gene, confirming the relation between allele s in the serotonin transporter gene and exposure to threatening life events in the onset of depression. The study proves, for a population sample accounting for gender, age and family history of psychiatric disorders, that 24% of the Spanish population, comprising people with the s/s genotype, need minimal exposure to threatening life events, unlike individuals with s/l or l/l genotypes, thus confirming the relation between genetic and environmental factors in this mental disorder.
Tailor-made antidepressants
The most important consequence of research on interaction between genetic and environmental factors is that, in a foreseeable future, scientists will be able to produce measures to predict response to antidepressants taking into account each individual's genotype, i. e. they will be able to design tailor-made drugs according to each person's genetic configuration and their exposure to environmental factors.
The research group headed by professor Cervilla Ballesteros and Gutiérrez Martínez is currently working at the University of Granada to open roads for psycho-pharmaco-genetics, a field that will allow for individual treatments, tailor-made drugs, for each patient with depression, a disorder affecting one in every five Spaniards visiting the doctor's.
This study is framed in the international project PREDICT and is funded by the European Union and the Spanish Ministry of Education and Science. One of its most important novelties is that it has been carried out through a very representative sample: a total of 737 people agreed to participate in the genetic tests, with ages ranging from 18 to 75, patients of nine primary care centres in the South of Spain. That is why this is the first representative population-based replication of earlier research, as until now research had been done into restricted population samples, comprising only women, adolescents, twins or people with affective disorders.
Contact: Professor Jorge Cervilla Ballesteros
Universidad de Granada
Multicenter study nets new lung tumor-suppressor gene
BOSTON–Collaborating scientists in Boston and North Carolina have found that a particular gene can block key steps of the lung cancer process in mice. The researchers report in the journal Nature that LKB1 is not only a "tumor-suppressor" gene for non-small cell lung cancer in mice, it also may be more powerful than other, better-known suppressors. The study will be published on the journal's Web site on Aug. 5 and later in a print version.
If further research shows LKB1 has a similar effect in human lung cells, it could influence the way non-small cell lung cancer is diagnosed and treated, says the study's senior author, Kwok-Kin Wong, MD, PhD, of Dana-Farber, one of three institutions, along with Massachusetts General Hospital and the University of North Carolina School of Medicine, leading the work. If tumors with LKB1 mutations are found to be especially fast-growing, for example, patients with such tumors might be candidates for more aggressive therapy.
People born with defective versions of LKB1 often develop Peutz-Jeghers syndrome, which is marked by intestinal growths and an increased risk for certain cancers. Non-inherited mutations of the gene have been found in some lung cancers. This suggested that LKB1 normally thwarts tumors from forming. Mutated versions may be unable to act as a brake on cancer.
To find out, the investigators ran a series of experiments in mice with a defective form of a gene called Kras, which drives the formation and growth of lung cancer. They tracked the development of lung cancer in animals with mutated LKB1 and compared it to the experience of animals with abnormalities in either of two well-known tumor-suppressor genes.
They found that while Kras "cooperated" with the mutated tumor-suppressor genes to produce lung cancer, it cooperated even more strongly with mutated LKB1. "The LKB1-deficient tumors grew more rapidly and spread more frequently than the others, and comprised all three types of non-small cell lung cancer — squamous cell carcinoma, large-cell carcinoma, and adenocarcinoma — rather than just one or two," Wong says. "This suggests that LKB1 plays a role at major stages of the tumors' development: initiation, differentiation of normal lung cells into cancer cells, and metastasis."
An examination of human non-small-cell lung tissue suggests LKB1 mutations play a role there as well. Of 144 samples analyzed, 34 percent of the lung adenocarcinomas and 19 percent of the squamous cell carcinomas contained abnormal versions of the gene, researchers report.
"We were surprised at how significant a role LKB1 mutations play in non-small cell lung cancer development in mice," say Wong, who is also an assistant professor of medicine at Harvard Medical School. "This suggests there may be additional lung tumor-suppressor genes yet to be discovered. We're currently examining whether these results apply to human lung cancers as well and, if so, how such information can improve treatment."
The lead author of the study was Hongbin Ji, PhD, of Dana-Farber. Other Dana-Farber co-authors include Dongpo Cai, PhD, Liang Chen, PhD, Pasi Janne, MD, PhD, Bruce Johnson, MD, Jussi Koivunen, MD, PhD, Danan Li, Mei-Chih Liang, PhD, Kate McNamara, Matthew Meyerson, MD, PhD, Samanthi Perera, PhD, Geoffrey Shapiro, MD, PhD, and Takeshi Shimamura, PhD. Other authors were based at Children's Hospital Boston, Brigham and Women's Hospital, Broad Institute of Harvard University and Massachusetts Institute of Technology, University of Tennessee Health Science Center, and the University of Texas Southwestern Medical Center.
The research was supported by the National Institutes of Health, the Sidney Kimmel Foundation for Cancer Research, the American Federation of Aging, the Joan Scarangello Foundation to Conquer Lung Cancer, the Flight Attendant Medical Research Institute, the Waxman Foundation, the Harvard Stem Cell Institute, and the Linda Verville Foundation.
Dana-Farber Cancer Institute (www.dana-farber.org) is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
Contact: Bill Schaller
Dana-Farber Cancer Institute
European heat waves double in length since 1880
The most accurate measures of European daily temperatures ever indicate that the length of heat waves on the continent has doubled and the frequency of extremely hot days has nearly tripled in the past century. The new data shows that many previous assessments of daily summer temperature change underestimated heat wave events in western Europe by approximately 30 percent.
Paul Della-Marta and a team of researchers at the University of Bern in Switzerland compiled evidence from 54 high-quality recording locations from Sweden to Croatia and report that heat waves last an average of 3 days now—with some lasting up to 4.5 days—compared to an average of around 1.5 days in 1880. The results are published 3 August in the Journal of Geophysical Research-Atmospheres, a publication of the American Geophysical Union. The researchers suggest that their conclusions contribute to growing evidence that western Europe's climate has become more extreme and confirm a previously hypothesized increase in the variance of daily summer temperatures since the 19th century.
The study adds evidence that heat waves, such as the devastating 2003 event in western Europe, are a likely sign of global warming; one that perhaps began as early as the 1950s, when their study showed some of the highest trends in summer mean temperature and summer temperature variance.
"These results add more evidence to the belief among climate scientists that western Europe will experience some of the highest environmental and social impacts of climate change and continue to experience devastating hot summers like the summer of 2003 more frequently in the future," Della-Marta said.
The authors note that temperature records were likely overestimated in the past, when thermometers were not kept in modern Stevenson screens, which are instrument shelters used to protect temperature sensors from outside influences that could alter its readings. The researchers corrected for this warm bias and other biases in the variability of daily summer temperatures and show that nearly 40 percent of the changes in the frequency of hot days are likely to be caused by increases in summer temperatures' variability. This finding demonstrates that even a small change in the variance of daily summer temperatures can radically enhance the number of extremely hot days.
"These findings provide observational support to climate modeling studies showing that European summer temperatures are particularly sensitive to global warming," Della-Marta said. "Due to complex reactions between the summer atmosphere and the land, the variability of summer temperatures is expected to [continue to] increase substantially by 2100."
The research was supported by the European Environment and Sustainable Development Program, the Swiss National Science Foundation and the National Center for Excellence in Climate Research (NCCR Climate).
Contact: Jonathan Lifland
American Geophysical Union
Identifying the mechanism behind a genetic susceptibility to type 2 diabetes
Type 2 diabetes is reaching epidemic proportions in the developed world. Determining if and how certain genes predispose individuals to type 2 diabetes is likely to lead to the development of new treatment strategies for individuals with the disease.
In a study appearing in the August issue of the Journal of Clinical Investigation Valeriya Lyssenko and colleagues from Lund University in Sweden show that certain variants of the gene TCF7L2 make individuals more susceptible to type 2 diabetes. The susceptibility variants were associated with increased expression of TCF7L2 in pancreatic islet cells and decreased islet cell secretion of insulin. Consistent with this, ectopic overexpression of TCF7L2 in human islet cells decreased insulin secretion in response to exposure to glucose. This study identifies TCF7L2 type 2 diabetes susceptibility variants and provides a mechanism by which these genetic variants might cause susceptibility to the disease. As discussed by the authors and in the accompanying commentary by Andrew Hattersley from Peninsula Medical School in the United Kingdom, future studies are likely to investigate the potential for manipulating the signaling pathways controlled by TCF7L2 for the development of new therapeutics for type 2 diabetes.
TITLE: Mechanisms by which common variants in the TCF7L2 gene increase risk of type 2 diabetes
Valeriya Lyssenko
Lund University, University Hospital Malma, Malma, Sweden.
Phone: 46-40-391214; Fax: 46-40-391222; E-mail: email@example.com.
View the PDF of this article at: https://www.the-jci.org/article.php?id=30706
TITLE: Prime suspect: the TCF7L2 gene and type 2 diabetes risk
Andrew T. Hattersley
Institute of Biomedical and Clinical Sciences, Peninsula Medical School, Exeter, United Kingdom.
Phone: 44-1392-406806; Fax: 44-1392-406767; E-mail: firstname.lastname@example.com.
View the PDF of this article at: https://www.the-jci.org/article.php?id=33077
Contact: Karen Honey
Journal of Clinical Investigation
U-M researchers find family of 'on switches' that cause prostate cancer
Gene fusions trigger cancer growth, could impact treatment choices
ANN ARBOR, Mich. — Researchers at the University of Michigan Comprehensive Cancer Center have discovered how genes turn on the switch that leads to prostate cancer.
The team discovered that pieces of two chromosomes can trade places with each other and cause two genes to fuse together. The fused genes then override the "off" switch that keeps cells from growing uncontrollably, causing prostate cancer to develop.
By testing these gene fusions in mice and in cell cultures, the researchers showed that the fusions are what cause prostate cancer to develop. But it's not just one set of genes that fuse. The researchers found that any one of several in a family of genes can become scrambled and fuse. Results of the study appear in the Aug. 2 issue of Nature.
"Each of these switches, or gene fusions, represent different molecular subtypes. This tells us there's not just one type of prostate cancer. It's a more complex disease and potentially needs to be treated differently in each patient," says lead study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology, a new U-M center whose goal is to translate research into real world practice.
The gene fusion research is the centerpiece project of the new center. In the current study, researchers found one of several abnormal gene fusions in the prostate cancer tissue samples they tested. In 2005, the researchers identified a prostate-specific gene called TMPRSS2, which fuses with either ERG or ETV1, two genes known to be involved in several types of cancer.
The Nature paper reports on five additional genes that fuse with ERG or ETV1 to cause prostate cancer. Gene fusions were involved in 60 percent to 70 percent of the prostate cancer cell lines the researchers looked at. The genes involved are all controlled by a different mechanism. For example, four of the genes are regulated by androgen, a male sex hormone known to fuel prostate cancer. Androgen deprivation is a common therapy for prostate cancer.
Knowing which gene fusion is involved in an individual patient's tumor could impact treatment options. If an androgen-regulated gene is involved, androgen therapy would be appropriate. But if the gene fusion involves a gene that represses androgen, the anti-androgen therapy could encourage the cancer's growth. This may also explain why androgen treatment is not effective for some prostate cancers.
"Typing someone's prostate cancer by gene fusion can affect the treatment given. We would not want to give androgen to someone whose prostate cancer gene fusion is not regulated by androgen," says Chinnaiyan, who is the S.P. Hicks Collegiate Professor of Pathology at the U-M Medical School.
Rearrangements in chromosomes and fused genes are known to play a role in blood cell cancers like leukemia and lymphoma, and in Ewing's sarcoma. A fused gene combination that plays a role in chronic myelogenous leukemia led researchers to develop the drug Gleevec, which has dramatically improved survival rates for that disease.
Chinnaiyan believes the prostate gene fusions will eventually lead to similar treatments for prostate cancer.
"More immediately, we hope to develop tests for diagnosis or prognosis. But long-term, we hope this will lead to better therapies to treat prostate cancer. The key challenge is to find a drug that would go after this gene fusion," Chinnaiyan says.
The gene fusion technology has been licensed to San Diego-based Gen-Probe Inc., which is working on a screening tool to detect gene fusions in urine. The tool could one day supplement or replace the prostate specific antigen, or PSA, test currently used to screen for prostate cancer.
The idea of translating laboratory research findings into a test or treatment that will impact patients is central to the new Michigan Center for Translational Pathology. The center brings together experts in genomics, proteomics and bioinformatics to look at common patterns and potential targets in cancer and other diseases. This is the first center of its kind in the nation in that it is associated with one of 39 National Cancer Institute-designated "comprehensive" cancer centers, a premier medical school and a large health system with both clinicians and patients.
The center's goal is to study the genes, proteins and other markers on cells to develop new diagnostic tests or screening tools as well as targeted treatments for cancer and other diseases, with the key being to translate these laboratory discoveries into clinical applications.
Chinnaiyan and his team have received numerous awards and honors, including the American Association for Cancer Research Team Science Award for their previously published work on gene fusions, and the Specialized Program of Research Excellence Outstanding Investigator award. The new Center for Translational Pathology supported in part by the Prostate Cancer Foundation, which has offered to match up to $1 million dollars in donations to support work related to developing therapies against prostate cancer gene fusions at the university.
"Mapping of the human genome was only the beginning. Equipped with the comprehensive analysis of the human genome, we can now systematically examine the blueprint of disease at the molecular level. This essential knowledge may lead to better diagnostic tests and promising new treatments for cancer, cardiovascular disease, diabetes and other illnesses," Chinnaiyan says.
For information about the Michigan Center for Translational Pathology, go to http://www.med.umich.edu/mctp.
About 218,890 men will be diagnosed with prostate cancer this year, and 27,050 will die from the disease, according to the American Cancer Society. The gene fusion work is not currently available for treatment or diagnosis, and no clinical trials are currently recruiting. For information about prostate cancer and currently available treatments, go to http://www.mcancer.org or call the U-M Cancer AnswerLine at 800-865-1125.
In addition to Chinnaiyan, U-M study authors were Scott Tomlins; Saravana Dhanasekaran, Ph.D.; Bharathi Laxman; Qi Cao; Beth Helgeson; Xuhong Cao; David Morris, M.D.; Anjana Menon; Xiaojun Jing; Bo Han; James Montie, M.D.; Kenneth Pienta, M.D.; Diane Roulston; Rajal Shah, M.D.; Sooryanarayana Varambally, Ph.D.; and Rohit Mehra, M.D. Mark Rubin, M.D., from Brigham and Women's Hospital, Dana-Farber Cancer Institute and Harvard Medical School is also a study author.
Funding for the study came from the U.S. Department of Defense, the National Institutes of Health, the Early Detection Research Network, the Prostate Cancer Foundation and Gen-Probe Inc.
The University of Michigan has filed for a patent on the detection of gene fusions in prostate cancer, on which Tomlins, Mehra, Rubin and Chinnaiyan are co-inventors. The diagnostic field of use has been licensed to Gen-Probe Inc. Chinnaiyan also has a sponsored research agreement with Gen-Probe; however, GenProbe has had no role in the design or experimentation of this study, nor has it participated in the writing of the manuscript.
Reference: Nature, Vol. 448, No. 7153, Aug. 2, 2007
Contact: Nicole Fawcett
University of Michigan Health System
Huntington's disease study shows animal models on target
This release is available in French.
An international team of researchers has published a benchmark study showing that gene expression in several animal models of Huntington's Disease (HD) closely resembles that of human HD patients.
The results, published August 1, 2007, in the , validate the applicability of using animal models to study human disease and will have important consequences for the pertinence of these models in preclinical drug testing.
Huntington's disease is an incurable and fatal hereditary neurodegenerative disorder caused by a mutation in the gene that encodes the huntingtin protein. Neurons in certain regions of the brain succumb to the effects of the altered protein, leading to severe motor, psychiatric, and cognitive decline. Several recent studies have shown that the mutant huntingtin protein modifies the transcriptional activity of genes in affected neurons. This disease mechanism is a promising new avenue for research into the causes of neuronal death and a novel potential approach for treatment.
Led by EPFL professor Ruth Luthi-Carter, and involving collaborators from six countries, the current study found a marked resemblance between the molecular etiology of neurons in animal models and neurons in patients with HD. This implies that animal models are relevant for studying human HD and testing potential treatments.
To come to this conclusion, the scientists measured the gene expression profile of seven different transgenic mouse models of HD, representing different conditions and disease stages. These profiles clarified the role of different forms and dosages of the protein hungtintin in the transcriptional activity of neurons. They then designed and implemented novel computational methods for quantifying similarities between RNA profiles that would allow for comparisons between the gene expression in mice and in human patients. "Interestingly, results of different testing strategies converged to show that several available models accurately recapitulate the molecular changes observed in human HD," explains Luthi-Carter. "It underlines the suitability of these animal models for preclinical testing of drugs that affect gene transcription in Huntington's Disease."
More Information:
EPFL Laboratory of functional neurogenomics, http://lngf.epfl.ch/
Alexandre Kuhn ; +41 21 693 1731
Professor Ruth Luthi-Carter; +41 21 693 9533
Contact: Alexandre Kuhn
Ecole Polytechnique Fédérale de Lausanne
Flip of genetic switch causes cancers in mice to self-destruct, Stanford researchers find
STANFORD, Calif. – Killing cancerous tumors isn't easy, as anyone who has suffered through chemotherapy can attest. But a new study in mice shows that switching off a single malfunctioning gene can halt the limitless division of tumor cells and turn them back to the path of their own planned obsolescence.
The surprising possibility that a cell's own natural mechanism for ensuring its mortality could be used to vanquish tumors opens the door to a new approach to developing drugs to treat cancer patients, according to Dean Felsher, MD, PhD, associate professor of medicine (oncology) and of pathology at the Stanford University School of Medicine. Felsher is the senior author of the study to be published July 30 in the advance online version of the Proceedings of the National Academy of Sciences.
"Our research implies that by shutting off a critical cancer gene, tumor cells can realize that they are broken and restore this physiologic fail-safe program," said Felsher.
Cancer can be notoriously resistant to medical treatment. Not only do cancer cells proliferate uncontrollably, they somehow circumvent the mechanism that causes normal cells to die when they get old or malfunction. That makes cancer cells effectively immortal unless doctors manage to squelch them.
The gene Felsher's team studied produces a protein called Myc (pronounced "mick"), which promotes cell division. A mutation of the gene causes cells to overproduce the protein, prompting perpetual cell division and tumor growth. By turning off the mutated gene, the researchers found that not only did uncontrolled cell division cease, but the cells also reactivated a normal physiological mechanism, called senescence, which makes it possible for a cell to eventually die.
"What was unexpected was just the fact that cancer cells had retained the ability to undergo senescence at all," said Felsher. Cancer researchers had long thought the senescence process had to be irreversibly disrupted for a tumor to develop.
The researchers worked with a series of mice engineered to have Myc-triggered cancers of either the liver, blood or bones, along with a specially constructed version of the Myc gene that they could switch off by feeding the mice antibiotics. When the mice dined on doses of the drugs, invariably, the tumors ceased growing and then diminished, with some disappearing over the course of just a few days.
Although Felsher's lab had previously shown that mouse tumors diminished and disappeared when Myc was switched off, they hadn't been sure how the process actually worked. Historically, most research involving genetic methods of battling cancer cells has focused on reactivating genes called tumor-suppressor genes, which are generally overcome by a proliferating cancer. No one had explored the idea that senescence might play a key role in diminishing tumors.
Felsher described senescence as acting like a fail-safe mechanism to stop cancer. When a cell detects a deleterious mutation, it launches the senescence process, resulting in the permanent loss of the cell's ability to proliferate, thus halting any cancer.
"In order to become tumor cells, those cells have to overcome senescence," said Chi-Hwa Wu, PhD, postdoctoral researcher in Felsher's lab and first author of the study. Wu had the inspiration to explore whether the sudden diminishment they had observed in the tumors might be due to the reactivation of some latent remnant of the trigger for senescence.
Through a series of experiments looking at enzymes associated with the senescence process, as well as some molecular markers, Wu confirmed her suspicion. And not only was senescence occurring in cells that had been thought to be incapable of it, the process was reactivated in all the different tumors they studied.
Consider it a cell version of the Jekyll-and-Hyde transformation. "It's sort of like Mr. Hyde realizing that there's something wrong with him and then being able to put himself back into his normal state as Dr. Jekyll," Felsher said.
In addition to the deepened understanding of how the process of senescence works, Felsher and Wu see a lot of potential for new approaches to treating cancer, beyond the traditional tactic of trying to kill cancer cells directly. "This work implies that maybe part of the strategy should involve figuring out how to get the cancer cells to just be allowed to do what they originally wanted to do anyway, which is to not be proliferating endlessly and growing uncontrolled," said Felsher.
The next step for the team is to see how well the approach works in human cancer cells. "And we're also trying to figure out what the mechanism is," Felsher said. "What are the molecular mechanisms of this, so that we can figure out how to better treat cancer""
Other authors on the research paper are Jan van Riggelen, PhD, postdoctoral researcher; Alper Yetil, graduate student in cancer biology; Alice Fan, MD, instructor in medicine (oncology), and medical student Pavan Bachireddy.
The study was funded by the National Cancer Institute, the National Institutes of Health, the Leukemia and Lymphoma Society, the Burroughs Wellcome Fund, the Damon Runyon Lilly Clinical Investigator Award, the Lymphoma Research Foundation and the Howard Hughes Medical Institute.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions – Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
Contact: Lou Bergeron
Stanford University Medical Center
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text:
Director Joe Wright's (Hanna) adaptation of the classic Leo Tolstoy novel Anna Karenina is gearing up for production. Focus Features will distribute the drama, which is set to star Keira Knightley, Jude Law, Aaron Johnson, Kelly Macdonald, Matthew Macfadyen, Emily Watson, and Domhnall Gleeson. The tragic love story follows Knightley as the title character, and the official synopsis is as follows:
The story unfolds in its original late-19th-century Russia high-society setting and powerfully explores the capacity for love that surges through the human heart, from the passion between adulterers to the bond between a mother and her children. As Anna (Ms. Knightley) questions her happiness, change comes to her family, friends, and community.
The film is set to begin production later this month in the U.K. and Russia, with an eye towards a fall/winter 2012 release date. Hit the jump to read the full press release.
Here's the full press release:
NEW YORK and LONDON, September 8th, 2011 – Joe Wright will direct the epic romance Anna Karenina, adapted from Leo Tolstoy's classic novel by Academy Award winner Tom Stoppard (Shakespeare in Love). The Working Title Films production will commence filming in the U.K. and Russia this month. Focus Features will distribute the movie domestically, and Universal Pictures International (UPI) will distribute the movie internationally, in the second half of 2012.
Anna Karenina marks Mr. Wright's third Working Title movie with Focus and UPI, following the award-winning boxoffice successes Pride & Prejudice and Atonement. Also for Working Title and UPI, he directed The Soloist; also for Focus, he most recently directed the hit adventure thriller Hanna.
Working Title co-chairs Tim Bevan and Eric Fellner are producing Anna Karenina with Paul Webster; the three were Academy Award nominees as the producers of Mr. Wright's Best Picture-nominated Atonement. Also with Focus, Mr. Webster was a Golden Globe Award nominee as producer of Eastern Promises.
Keira Knightley, Academy Award-nominated for Pride & Prejudice, will star as Anna Karenina in her third collaboration with Mr. Wright. Ms. Knightley will be starring opposite two-time Academy Award nominee Jude Law, as Anna's husband Aleksei Karenin; and Aaron Johnson (Nowhere Boy), as Count Vronsky. Rounding out the cast will be Kelly Macdonald (Boardwalk Empire), Matthew Macfadyen (Pride & Prejudice), Domhnall Gleeson (Harry Potter and the Deathly Hallows), Alicia Vikander (The Seventh Son), two-time Academy Award nominee Emily Watson, Olivia Williams (Hanna), and Ruth Wilson (Luther).
Also reteaming with Mr. Wright on Anna Karenina are Academy Award-winning composer Dario Marianelli, twice-Academy Award-nominated costume designer Jacqueline Durran, and three-time Academy Award-nominated production designer Sarah Greenwood. The cinematographer will be Academy Award winner Philippe Rousselot. Melanie Ann Oliver (Focus' Jane Eyre) will edit the feature. Sidi Larbi Cherkaoui will be the choreographer on the movie.
The story unfolds in its original late-19th-century Russia high-society setting and powerfully explores the capacity for love that surges through the human heart, from the passion between adulterers to the bond between a mother and her children. As Anna (Ms. Knightley) questions her happiness, change comes to her family, friends, and community.
Focus Features CEO James Schamus said, "Joe Wright is a master filmmaker, and with Tom Stoppard's brilliant screenplay this Anna Karenina will be full of both pageantry and emotion. To realize Joe's vision, we have the perfect producing partners in Working Title and Paul Webster, whose acumen is unsurpassed. With Keira Knightley playing this iconic role and a splendid cast supporting her, today's moviegoers will be drawn to this powerful story."
Mr. Bevan commented, "Everyone at Working Title is proud to affirm a longtime collaboration with Joe Wright through this, our fourth picture together. That we are able to re-convene cast and crew from Pride & Prejudice and Atonement makes it all the more exciting. We anticipate that this will be a defining screen version of Anna Karenina."

subset: commoncrawl


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Fachbereich Mathematik
We discuss how kinetic and aerodynamic descriptions of a gas can be matched at some prescribed boundary. The boundary (matching) conditions arise from requirement that the relevant moments (p,u,...) of the particle density function be continuous at the boundary, and from the requirement that the closure relation, by which the aerodynamic equations (holding on one side of the boundary) arise from the kinetic equation (holding on the other side), be satisfied at the boundary. We do a case study involving the Knudsen gas equation on one side and a system involving the Burgers equation on the other side in section 2, and a discussion for the coupling of the full Boltzmann equation with the compressible Navier-Stokes equations in section 3.
In these lectures we will mainly treat a billard game. Our particles will be hard spheres. Not always: We will also touch cases, where particles have interior energies due to rotation or vibration, which they exchange in a collision, and we will talk about chemical reactions happening during a collision. But many essential aspects occur already in the billard case which will be therefore paradigmatic. I do not know enough about semiconductors to handle collisions there - the Boltzmann case is certainly different but may give some idea even for the other cases.


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The main Capture One User Interface elements are a Tool Tab bar, the Viewer and Image Browser.
Capture One provides a wide range of possible ways to view and inspect images. Users can customize the Image Viewer and the Image Browser to fit the needs of your particular workflow.
The interface is divided into a number of elements, all providing a set of tools. The Toolbar provides graphical shortcuts to some of the most useful functions of Capture One.
Each Tool Tab contains a number of utilities that include a set of tools to adjust image files.


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Ready for Space!
Early this morning, one o'clock local time, I eventually completed my private Notebook. So now I am by definition ready. Ready for Space! Earlier in the day we were able to be with our respective partners for a few hours and especially to show them around the launch tower. It was enormous fun for both them and us.
Later Nick and I were in the cockpit for an hour in order to check that all the cable connections to the TV, laptops etc. were in the correct positions. It was also an excellent opportunity to look around a little and become familiar with the unusual vertical orientation.
ESA had a big reception at Cocoa Beach, where all the launch guests were present, around 400 according to the information. I was able to telephone there and talk to the most distinguished guests (which of course included Lisa!). The mood seemed very good. Everything technically is still "GO" for launching today and just recently the movable part covering Discovery itself was swung away. Now it is mostly up to the weather gods. The latest forecast gave only a 40% chance of launching, but we will most likely all jump into Discovery tomorrow anyway and then see how it goes.


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This post was written back on May 24, 2010. I never got around to post it.
I am posting it because Stephen Dawson, a 4th cousin, wrote a comment yesterday on my blog. I have never him, but Stephen is the reason why I write this blog just like Alyce LaGasse was the reason back in 2010.
In my book she is as famous as Emeril Lagasse…
She said once I was amazing with all my research about her roots.
I told her she was amazing also.
Alyce is the one who found some of Samuel LaGasse's descendants. Samuel was her father's brother.
She went on the Internet and she found a clue, then she acted on it.
With that information I could identify the people on this picture…
Back in 2010, I contacted the son of the little girl on the left, and he sent this on his Facebook to give his mother…
Claudette is the little girl on the left on this picture.
Dorothy, Stephen's mother, is on the right.
Stephen is the reason why I will keep on writing this blog and keep sharing.


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I would not put much faith in those rumors for now (D750?) but I still find them interesting, especially the Nikon D750 back image: FF with swivel display - now this will trigger some serious discussions here 🙂
What say you - do you like this D750 with the swivel display and how much would you pay for such a camera?
Via Digitalrev


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Create an Account - Increase your productivity, customize your experience, and engage in information you care about.
These are printable PDFs. Most of them are letter-sized. Some are tiled map books. Most of the information in these paper maps is also available in the interactive GIS maps, and most of the interactive maps have a print option.


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By virtue of the power of sale contained in a Deed to Secure Debt by James O. Fletcher and Janie Fletcher to Travelers Bank & Trust, FSB, dated January 20, 1999 and filed for record January 26, 1999 in Deed Book 321, Page 558, Appling County, Georgia records, and securing a Note in the original principal amount of $26,756.20, there will be sold at a public outcry for cash to the highest bidder before the Courthouse door of Appling County, Georgia, between the legal hours of sale on the first Tuesday in November, 2011, by CitiCorp Trust Bank, FSB formerly known as Travelers Bank & Trust, FSB as Attorney-in-Fact for James O. Fletcher and Janie Fletcher the following property to-wit:
ALL THAT PARCEL of land in Second Land District, Appling County, State of Georgia, consisting of (1) acre of Lot of Land No. 370 and being bound now or formerly as follows:
North by a graded road; east and south by lands of Clara Fletcher; and west by lands of Pauline Phillips, said lands being accurately described according to a survey and plat thereof by Olin J. Baxley, County Surveyor, dated January 5, 1959, said plat being of record in the Office of the Clerk of Superior Court, Appling County, Georgia, in Plat Book 3, Page 370, reference being made to said plat for all purposes.
The above-described property is also known as 1312 Fletcher Road, Baxley, GA 31513.
The indebtedness secured by said Deed to Secure Debt having been declared due and payable because of default in the payment of the indebtedness secured thereby, this sale will be made for the purpose of paying the same and all expenses of sale, including attorney's fees, if applicable.
The property will be sold as the property of the aforesaid grantor subject to the following: all prior restrictive covenants, easements, rights-of-way, security deeds, or encumbrances of record; all valid zoning ordinances; matters which would be disclosed by an accurate survey of the property or by any inspection of the property;? all outstanding taxes, assessments, unpaid bills, charges, and expenses that are a lien against the property whether due and payable or not yet due and payable.
To the best of the undersigned's knowledge and belief, possession of the subject property is held by Janie Fletcher and James O. Fletcher.
Pursuant to O.C.G.A. § 44-14-162.2, the name, address and telephone number of the individual or entity who shall have the full authority to negotiate, amend or modify all terms of the above described mortgage is as follows:
CitiMortgage, Inc.
5280 Corporate Drive
Attn: Default Mail Services
Frederick, MD 21703
Phone: HAT Program: 866-272-4749
Fax: 866-989-2089 or 866-989-2088
The foregoing notwithstanding, nothing in O.C.G.A. ? 44-14-162.2 shall be construed to require CitiCorp Trust Bank, FSB to negotiate, amend or modify the terms of the Deed to Secure Debt described herein.
CitiCorp Trust Bank, FSB formerly known as Travelers Bank & Trust, FSB
as Attorney-in-Fact for
James O. Fletcher and Janie Fletcher
By: S. Andrew Shuping, Jr.
S. Andrew Shuping, Jr.
6259 Riverdale Road, Suite 100
Riverdale, Georgia 30274-1698
(770) 991-0000
10-5, 10-12, 10-19 & 10-26ch
gpn11 NOTICE OF SALE UNDER POWER
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One of my favorite young pitchers in baseball right now is White Sox lefty John Danks. His minor league track record was rather strange, and he's a great candidate for a retrospective prospect examination. …
White Sox pitching coach Don Cooper taught Danks to throw a cutter (cut fastball) after his 1st year in the majors.
Danks started working on it during the 2007 season:
Danks has been gradually trying to add a cut fastball into his pitching repertoire.His work on this particular pitch began during regular-season side sessions and still is in its early stages, a steep learning curve that can be frustrating at times.
"I'm the type of guy who wants results right away, but it's a pitch I've never thrown before," said Danks of learning the cutter. "I'm still kind of experimenting with different ways to hold the ball and how to throw it.
"Coop [White Sox pitching coach Don Cooper] sees me getting frustrated and reminds me it won't happen overnight. It might take a while, and it's still a work in progress, for sure."
Danks has not been comfortable enough to use the new pitch in a game, basically experimenting with the cutter during three different side sessions and when he plays catch every day. But the 22-year-old understands how effective the pitch can be once it is mastered simply by watching fellow southpaw Mark Buehrle in action.
"Mark's funny, because he's one of those guys where he's so good, he doesn't know how he does it," said Danks of Buehrle, who has been lending his expertise to Danks in regard to the new pitch.
As he stands presently, Danks throws his sinker inside to left-handed hitters, but primarily uses a four-seam fastball in the same situation to a righty. The cutter will give Danks something that comes in a littler harder to a right-hander.
"It might look like a good fastball to hit and jam a righty," said Danks, who planned to work with John Wetteland on the pitch in Texas, before Wetteland left for Washington. "It's really just another weapon against right-handed hitters.
"When I do get it ironed out, it will be a big part of my pitching style. I'm excited to work on it now because it will help a lot."
and started throwing it in the 2008 season:
Danks does enter competition with an extra weapon, though, a cutter that he began working on last year and has been throwing impressively through the first week of bullpen sessions and batting practice.That particular pitch gets a little more practical use during Wednesday's contest.
"Exactly," said Danks of using the cutters to challenge hitters in live-game action. "It's a good read to see how hitters react to it, and if I can throw it for strikes consistently. So far it has been great, and I feel real comfortable with the pitch.
"I was working on it all last year, and I took what [pitching coach Don Cooper] told me and ran with it. It's a pitch to get in on the right-handed hitters. I didn't have anything to get in on them and keep them honest on the inner half."
You can see it on Danks fangraphs pitch types too.


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I have rev 2 of BW9 and am using the Public Review version of BW9 for Mac.
1. I have recently upgraded my OS to Maverick and reinstalled my BW9 for Mac Public Review. When I run BW9, it will automatically quit on its own, saying "Housing cleaning". What is going on and how do I correct this issue?
2. What are my options to update the Mac installer? Can I update directly from my Public Review version or do I have to purchase the installer?


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According to the New York Post, Weintraub has Tony Award winner Hugh Jackman in mind for the project, although no director or writer are attached.
"Behind the Candelabra," which starred Michael Douglas and Matt Damon, premiered at the 2013 Cannes Film Festival May 21 and aired on HBO May 26. The film was adapted from Thorson's memoir "Behind the Candelabra: My Life With Liberace" by Richard LaGravenese, who is directing the upcoming film adaptation of The Last Five Years, and featured music by the late Marvin Hamlisch.
No official announcement about a Broadway production has been made.


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One of Nature's most wonderful gifts, honey is produced by bees through collecting nectar from flowers - simulataneously pollenating plants as they go.
It's one of the most beautiful virtuous circles our amazing planet has to offer.
Amazingly, to produce a single jar of honey, the foraging bees have to travel extraordinary distances - perhaps as much as three times around our planet.
Pukka's honey comes from sustainable organic hives - giving us the purest form of sweetness you can imagine.


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The safest place in the world for you is curled up on the
companion's tomb.
In the figs above your sleeping, there is a nest.
The tender man sells sweets. Here the veil between worlds
shimmers thinnest.
Your mother reached out, caught the smallest feather in the
air. Each year she made two
new pillows. Your father, at the mosque, hand-fed a turkey
The turkey, fat already, jumped over the wall and into the city
with at least three names.
Through the ancient streets he wandered to the sweet seller
who read prayers into the air.
You recall how other times you took yourselves to caves.
Elsewhere you read over and over The Throne.
When oppression exists, even the bird dies in its nest.
My sweet, sweet love, today they bombed this place.
On the news I saw an eight-year-old digging graves.
Christi Kramer is a graduate of George Mason University's Creative Writing program. This poem is from Reading The Throne, an ethnography-in-poetry of Iraqi Kurds exiled and living in Harrisonburg, Virginia.


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Imagine Being Suffocated by Artistic Brilliance, and Loving It!
What was Tim Mantoani's Exhibit on the Artists behind our World's Most Iconic Photographs as he Exposes the Intimate Personalities behind their Legendary Photos
Done Masterfully in Mammoth 20X24 Polaroid Format
This week, Manhattan was honored to host the most anticipated event to thousands of photo talents worldwide- all who attended the PhotoPlus Expo at the beautiful Javit's Center. There, the industry's highly esteemed photographer Tim Mantoani unveiled his latest book 'Behind Photographs – Archival Photographic Legends' – an sexy, intimate glance at what's to see on the other side of the lens- leaving you craving more of the underrattedly engaging 'behind the scenes' footage. Twenty of the book's featured Icons attended the celebratory wine tasting and photo exhibition at one of the City's most engaging cultural hotspots – the Ogilvy & Mather's Eye Patch Productions- to pay their respects to the artist who see's them as his muse. Perhaps never again will so many legendary photographers be under the same roof – the energy was inspiring and contagious! The event proved to be the creative heartbeat of the city that night & the premere event of the entire Expo, as it opened to its 300+ devoted attendees (who toughed it out in pouring rain to be there) at 7:00pm till 9:00pm to experience the artistic brilliance the exhibit bred. Executed by the always impressive TheBarnYardGroup, the event's set-up is superb; Mantoani's exhibit is an enthralling experience as huge, larger-than-life portraits drapes the event space and excites anyone who is lucky to experience it.
Never has there been so much talent in the field of Artistic Photography in one room than ever before- imagine being suffocated by artistic genius, and liking it! The talent and brilliance of so many Iconic, successful photographers in one space has proved to be more potent to the attendees than, dare I say, anyone has ever experienced prior! Many of Mantoani's featured Icons had confirmed to attendin advance- setting the guest list on fire! The evening included such great names as (but definitely weren't limited too: Eric Meola; Kristin Ashburn; Barbara Bordnick; John Dominis; Douglas Dubler; Jeff Dunas; Jill Enfield; Bill Eppridge; Donna Ferrato; Carl Fischer; Deanne Fitzmaurice; Lynn Goldsmith ;Greg Gorman; Keith Green; Lois Greenfield; Michael Grecco; Fred Gurner; John Iacono; Guido Karp; Ed Keating: Douglas Kirkland; Dan Kramer; Elliott Landy; Roxanne Lowitt; Gerd Ludwig; Thom Mangelsen; Joe McNally; Lyle Owerko; May Pang; the Sandro; Brian Smith; Ian Macdonald Smith; Art Strieber; and Linda Troeller and the Greg Watermann Group.Linda Troeller and the Greg Watermann Group. Photos and interviews are available for press at the event by contacting [email protected] for copies.
'Behind Photographs – Archival Photographic Legends' is Mantoani's personal mission to introduce the world to the photographers behind some of the world's most quintessential images. Reviving the use of the rare and mammoth format of 20X24 Polaroid, Mantoani gets familiar with all his featured photographers in a very individualistic portrait- holding their personal favorite or most iconic photograph. Mantoani is a fiery revolutionary in bringing photography back to its classic, primal roots- resurrecting the use of old school Polaroid's and exposing the hidden face of the photographers behind the famous pictures. And to every successful revolutionary follows a revolution! The Polaroid-look has been reborn in American culture and the classic, over exposed look is the hottest trend right now. The evidence is undenialable: Polaroid-like advertisments can be seen in Urban Outfitters, American Apperal and other brand label stores everywhere. Such places are selling the trendy knock off Polaroid camera, along with promoting the urban, retro fashion look the Polaroid represents. And you know anything is hot when international rock goddess Lady GaGa makes her fine self out as the brands spokes model - as she has with Polaroid. Other trends like the iPhone Hipstimatic application are wildly popular in today's high-tech culture; a iPod and iPad case is sold at the Apple store that mimics the look of a Polaroid camera- proving that our culture apprciates the retro Poloroid look as much as they apprciate the beauty of a high tech Apple product. Hipstimatic is the ideal example of the Polaroid fusion with our modern world- Hipstimatic prints are seen everywhere on the Facebook scene- with such massive exposure, Facebook has carried that Polaroid spirit from New York City to Los Angeles. Its also become a hit look in the ad biz in creating a sexy, almost 'forbidden - fruit' type allure for a variety of products such as Absolut Vodka and many others.
Mantoani and the other 150 Icons shot in this book beautifully represent the fusion of appreciation for sleek modern technology and the celebration of the beautiful, primal it was born of- the book in itself is the ultimate Icon of the evolution of photography. Exactly this is the revolutionary Mantoanis purpose- using his respected identity and fabulous event to serve as a platform to ignite his Revolution - the shot heard around the art world! He aims to bring a variety of photographers together to create a studio setting for photographers to embrace and be inspired by the evolution of their craft- the camera. It will also include a non-profit educational role that allows students everywhere to make this part of their way forward.
Like pictures, which are forever still glimpses into the past, Mantoani believes the photographer themselves should be immortalized: "I have been shooting portraits of photographer's for the past five years on 20×24 Polaroid. As many of these photographers, like Polaroid, fade away, I hope these images will be a way for future generations to appreciate the contribution these artists have made", said Mantoani.
Featured photographers include legendary rock photographer Jim Marshall holding a photograph of the late Johnny Cash during his legendary concert at San Quentin Prison; Neil Leifer posing with his famous shot of Muhammad Ali standing and gesturing over a knocked out Sonny Liston; Harry Benson with his epic photo of The Beatles having a pillow fight; and Steve McCurry's famed portrait of the Afghan Girl from the cover of National Geographic- to name an impressive few. What makes the portraits extremely intimate however is that at the bottom of each Polaroid, the photographer has written a personal comment about their image in their own penmanship- immortalizing both photographer and their vision in the portrait.
The genesis of "Behind Photographs" came in 2006 when Jim Marshall met up with Mantoani in San Francisco with a portfolio of classic images of Jimi Hendrix, Bob Dylan and Johnny Cash and recounted the stories behind each image. "I remember having several sleepless nights as I re-lived the shoots in my mind. I found the process, the camera, and the images simply magical. I began thinking of whom else I could photograph and how this body of work could stand to be an important historical documentation and a way for future generations to be able to not just appreciate famous images, but the photographers as well."
About the Artist: Tim Mantoani is a San Diego based photographer. His credits include Sports Illustrated, Newsweek and ESPN the Magazine, as well as ad campaigns for Coca-Cola, EA Sports and Coors Brewing. Today, when Tim's not shooting on assignment, he's documenting other honored lens men who have collectively captured decades of culture and celebrity with their own cameras. Each image features a photographer holding their most iconic or favorite image. Legendary rock photographers Jim Marshall and Ethan Russell have sat for 20 x 24-inch Polaroid portraits, as have Walter Looss, Steve McCurry, Mary Ellen Mark, Elliott Erwitt and Roberto Salas. Tim's enthusiasm for the medium of photography is undiminished by the changes he's seen during his career. For him it's not work so much as a mission: He sees the story there in each face and in each place and lives to gives them voice through his work.
View Tim Mantoani's webpage here: Behind Photographs - Archival Photos
About the PDN PhotoPlus International Conference + Expo: Regarded as the most important event in the photo industry, the PDN PhotoPlus International Conference + Expo is especially designed for professionals and advanced amateurs in the photographic and imaging industries- unfailing to always feature the most recent and exciting advances in photography.Photo District News (PDN), the award-winning monthly magazine for the professional photographer, has been covering the professional photographic industry for almost three decades and his wisdom and passion for his craft is the foundation for the highly esteemed event. Held annually at the Jacob K. Javits Convention Center, the PDN PhotoPlus Expo offers a special opportunity to its attendees, who are able to explore hundreds of exhibits and attend a wide variety of photography and imaging seminars that are an unparalleled experience in the photo industry.
"Behind Photographs" is published by Channel Photographic, and retails for $60.00. It will be in bookstores by the end of November. For more information on the book and a behind-the-scenes look at the creation of the book please visit http://www.mantoani.com/ or contact Donnetta Campbell to join / partner with us and to help save the Polaroid Movement 646.532.1512.
Seen Above: To join the Revolution that is stirring to save the Polaroid & Support Tim Mantoani's Vision, Get involved at Kickstarter!
Linda Troeller and the Greg Watermann Group. Photos and interviews are available for press at the event by contacting [email protected] for copies.
Linda Troeller and the Greg Watermann Group. Photos and interviews are available for press at the event by contacting [email protected] for copies.
Linda Troeller and the Greg Watermann Group. Photos and interviews are available for press at the event by contacting [email protected] for copies.


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The new Plant!t Aeros is a sleek and stylish purpose-made DWC
The new Gavita Pro line e-series complete fixtures are next generation professional grow light solutions.
CANNA AkTRIvator granule soil mix - protect your plants with friendly fungi!
The entire range of products has been designed, manufactured and bottled in Holland.
9994 in stock


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Artwork description:
This is one of the images from my 'Fabstract' collection. It is based on the concept of capturing an abstract impressionist mood or moment in time of the Yorkshire and Cumbrian landscapes. Throughout the series there is a sense of beauty and drama with an epic vastness, a calm tranquility and a kind of mystery. Leaving parts to the imagination of the viewer to ponder over, Fabstract is a truly curious collection of studies involved in the topographical subject of outdoor space, light and mood.
Working closely with a member of the Fine Art Trade Guild, I will supply this original limited edition 1 of 1 print as a Giclee print onto 315gsm archival canvas, using the best longevity inks. The final printed size (1339 x 884mm) will include a 3 inch plain border all around the image so that it can be framed without any loss of image.
The artwork will be packed very carefully - rolled and bubble-wrapped, inside large diameter toughened cardboard tubes, to ensure that it reaches you in perfect condition.
Materials used:
Digital painting
#landscape #contemporary art #water #black #minimalist #dark #moody #waterfall
Jet Black (2018)
Digital Art (Giclée) by Simon Antony Wilson
$3,791Free shipping
- Digital Art (Giclée) on Canvas
- From a limited edition of 1
- Size: 52.72 x 34.8 x 0.12 in (unframed) / 46.81 x 28.9 in (actual image size)
- Signed and numbered certificate of authenticity
- Style: Impressionistic
- Subject: Landscapes, sea and sky
- Hurry only 1 left in stock
This artwork is sold by Simon Antony Wilson from United Kingdom


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At long last we have an official trailer for "Beats, Rhymes & Life: The Travels of a Tribe Called Quest," Michael Rappaport's documentary about one of rap's best and most important bands.
We were lucky enough to catch the film at the Tribeca Film Festival last month, and enjoyed immensely. The tension between QTip and Phife Dawg makes for great theater at times, with Rappaport actually catching one of their blow-ups on camera.
U.S. & World
The day's top national and international news.
"Beats, Rhymes & Life: The Travels of a Tribe Called Quest" opens July 8 in New York and Los Angeles.


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With director Steven Soderbergh's spy-action pic Haywire opening tomorrow, I recently got to speak with most of the cast about making the movie. Starring MMA fighter Gina Carano as a burned spy who takes revenge against her handlers, Haywire also stars Channing Tatum, Michael Fassbender, Ewan McGregor, Michael Angarano, Antonio Banderas, Michael Douglas, and Bill Paxton. I've seen Haywire twice now and it's fantastic. On top of Carano's star-making performance, the action scenes are some of the best I've seen in years. It's absolutely something you should see in a theater.
During the press junket I got to speak to Channing Tatum twice. The first time we just talked about Haywire. However, the second time we covered a ton of other topics like what the last year has been like for him, his relationship with Soderbergh, how Magic Mike came together and it's rating, what it was like working with Matthew McConaughey, and what happened to The Man from U.N.C.L.E.. In addition, Tatum revealed he has a small part in Soderbergh's next picture, The Bitter Pill (which might now be called The Side Effects), and we ended talking about Bennett Miller's Foxcatcher – which he might star in with Steve Carell. It's a crazy sounding movie. Hit the jump to watch.
- 0:25 – Reflects on his work over the last year, which he called "a grind."
- 1:05 – Talks about Steven Soderbergh and working with him on Haywire.
- 2:05 – Has picked up an appreciation of the finer points of rounding out a character as an actor and making that character work within the overall framework of the film.
- 3:30 – Talks about Magic Mike and his real life experience as a stripper at the age of 18. Says, "If you ever wanted to know what it was like to be a male stripper, this is it."
- 4:25 – Discusses Magic Mike being rated "Hard R" and why it has to be that way.
- 5:35 – Talks about Magic Mike being primarily a "fun movie" and discusses Soderbergh's style.
- 6:10 – Gives background on characters in Magic Mike and talks about whether or not they're based on real people.
- 7:10 – Jokes about the ratio of "amount of time Matthew McConaughey is shirtless in a movie vs how much money the movie makes." Candidly talks about McConaughey as an underrated actor and compares his commitment to that of Al Pacino.
- 8:40 – Talks about getting McConaughey for the movie because he sees him as a sort of Mad Hatter and says that McConaughey transcends the character that was written for him.
- 9:25 – Dismisses the rumor that he and Soderbergh were working on Man from U.N.C.L.E. and says the project fell through due to budgetary issues.
- 10:05 – Comments briefly that he has a small part in Soderbergh's next picture, The Bitter Pill.
- 10:10 – Calls Foxcatcher a "beautifully insane and dark tale" and discusses a brief synopsis of it. Says it's Bennett Miller being "back to form."
- 10:55 – Talks about Steve Carell playing John du Pont in Foxcatcher and discusses the character dynamics. Says he "can't wait for Carell to try something more heavy and serious."


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Top flight deals to Havana (HAV)*
Fly to Havana with KLM
Together with our global network, KLM Royal Dutch Airlines offers flights to Havana, serving Havana Jose Marti International Airport (HAV). Be prepared for your next trip to Havana: don't forget to pack a thing with KLM's pack assistant! You will be fully prepared as KLM brings you smart and personalised packing lists for all KLM destinations. Because we believe that stress-free travel starts at home!
KLM Destinations: Havana, Cuba
Top Havana attractions
- Old Havana: the beating heart of Havana, founded in 1519, and a UNESCO World Heritage site.
- El Malecon: a broad promenade stretching along the coastline and the perfect spot for an evening stroll.
- El Morro: the fortress guarding the entrance to Havana bay, once the location of a school for lighthouse keepers.
- Fusterlandia: an unusual folk-art kingdom, the reclaimed childhood neighbourhood of Cuban artist, José Fuster.
- Playas de Esta: a beautiful beach strip, visit for the best sun, sea, and sand that Cuba has to offer.
For all of the best hotspots, accommodation ideas and tips and tricks, take a look at our in-depth travel guide. It's all you need to live like a local and get the most out of your trip to Havana!
What's the best way to get around Havana?
Havana is dominated by pedestrians as on foot is the best way to navigate the old town streets and alleys. If you do hire a vehicle, you'll find the roads to be quiet as most locals walk. There are plenty of buses that run frequently, but as most residents don't have cars, you'll find they can get very crowded during peak hours.
What's the weather in Havana?
Havana's temperature stays fairly consistent year-round. Temperatures average between 21°C (70°F) in January and 27°C (81°F) in July. May through to October see heavy rainfall so it may be best to travel during other seasons if you prefer to stay dry.
Weather in Havana
Powered by: OpenWeatherMap.org
29 °CSaturday15/08/2020
31 °CSunday16/08/2020
31 °CMonday17/08/2020
30 °CTuesday18/08/2020
31 °CWednesday19/08/2020
31 °CThursday20/08/2020
31 °CFriday21/08/2020
*All amounts are in HUF. Taxes and carrier surcharges included. No booking fee applicable.


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Nearly a year after its release, Norah Jones' Come Away with Me nabbed the #1 spot on the Billboard album chart. A month later, it would win the Grammy for Album of the Year. It would go on to sell 10 million copies in the United States and 22.5 million worldwide.
Her voice, which "is mature beyond her 22 years," MR has "a touch of Rickie Lee Jones" DA while the arrangements suggest a touch of Bonnie Raitt. DA "Her youth and her piano skills could lead one to call her an Alicia Keys for grown-ups." DA "Her assured phrasing and precise time are more often found in older singers as well. She is instantly recognizable, blending shades of Billie Holiday and Nina Simone without sounding like anyone but herself. Any way you slice it, she is a singer to be reckoned with." MR
Her "debut on Blue Note is a mellow, acoustic pop affair with soul and country overtones, immaculately produced by the great Arif Mardin." DA "Jones is not quite a jazz singer, but she is joined by some highly regarded jazz talent: guitarists Adam Levy, Adam Rogers, Tony Scherr, Bill Frisell, and Kevin Breit; drummers Brian Blade, Dan Rieser, and Kenny Wolleson; organist Sam Yahel; accordionist Rob Burger; and violinist Jenny Scheinman." DA
Jones does "convincing readings of Hank Williams' Cold Cold Heart, J.D. Loudermilk's Turn Me On, and Hoagy Carmichael's The Nearness of You." DA "Heart" and "Nearness" alone "are worth the price of the CD." MR
"Her regular guitarist and bassist, Jesse Harris and Lee Alexander, respectively, play on every track and also serve as the chief songwriters. Both have a gift for melody, simple yet elegant progressions, and evocative lyrics." DA "Jones, for her part, wrote the title track and the pretty but slightly restless Nightingale." DA Her material, "while not bad, pales a bit next to such masterpieces. They might have fared better had she…opted for some livelier arrangements" MR "or if the tunes had simply been given less laconic performances." MR Still, "while the mood of this record stagnates after a few songs, it does give a strong indication of Jones' alluring talents." DA She "has all the tools; what will come with experience and some careful listening to artists like J.J. Cale and Shirley Horn is the knack of remaining low-key without sounding sleepy – sometimes less is not, in fact, more." MR
- one of the top 1000 albums of all time
- one of the top 100 All-Time World's Bestsellers>
- Grammy Award for Album of the Year
- Grammy Award for Pop Vocal Album of the Year
- Rock and Roll Hall of Fame
- Top 30 Jazz Albums of All Time
- top 100 albums of the 2000s
Resources and Related Links:
- the DMDB page for Come Away with Me
- the DMDB Music Maker Encyclopedia entry for Norah Jones
- DA David R. Adler, All Music Guide
- MR Michael Ross, Amazon.com


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Champions crowned at Junior Olympic National Cross Country Championships
Provided by USATF
SAN ANTONIO - Champions were crowned in six age groups at the 2013 Junior Olympic National Cross Country Championships in San Antonio, Texas, Saturday afternoon. More than 3,400 young athletes from 16 regions competed on the course at the National Shooting Complex.
The athletes competing in the national championship qualified through their respective state and regional competitions with races divided by age group. Each division competed according to the following distances: 8-and-under racing 2 km; 9-10 racing 3 km; 11-12 racing 3 km; 13-14 racing 4 km; 15-16 racing 5 km; and 17-18 racing 5 km.
Appropriately sunny for the opening race, the 8 & under girls were first to take the course.
Mackenzie Brown of the Lions Track Club was the day's first finisher, crossing in 7:30.98 to take the 2 km title in the 8-under age group. In second with a time of 7:35.98 was Leah Futey of the Cougar Track Club followed by teammate Cecilia Campos who finished in 7:54.93 to take third.
In the boys 8-under race, Dennis Sachek of Town Track Club narrowly edged out the the unattached Owen Tighe and Liam Olson of Valley Track Club as the three finished the 2 km in 8:27.46, 8:27.58 and 8:27.92 respectively.
Aidyn Woodall of the Parker Panthers took first in the 9-10 girls 3 km, coming in at 11:02.7. Texastron's Eva Jess was a close second with her 11:04.29 finish, and Alexis Fernandez rounded out the top three in 11:06.34.
From Forr XC, James Donahue's 10:44.64 performance led the 9-10 boys division as Brandon Howell finished second in 10:52.35, nosing ahead of Azaan Dawson, who finished in 10:53.15 for third.
The 11-12 girls excited spectators with Devianna Salcedo breaking away from the field to cross in 10:28.66. Angela Saidma of Wilton Running Club and Lauren Robinson of Nashua PAL Gate City Striders fought to the finish, producing the day's first-and-only tie when they crossed in 10:42.68.
Also breaking away was Joseph Waskom of Speed Unlimited who crossed in 9:41.49. Samuel Toolin's 9:52.17 earned second for Sentinel A, and Thomas Gastineau came in at 10:06.14 for Indiana.
Marianne Abdalah from Wings of Moon may have finished last year's race as runner-up, but she proved herself victorious in the 13-14 girls division with her time of 14:15.69.
"I knew I had something to prove to myself," said Abdalah. "I had to pace myself at the start and kick at the right time. It was redemption to win today."
Taylor Roe, running unattached, took second in 14:34.54 and said, " I knew it would be tough competition." Sofia Castiglioni, who earned third with her time of 14:36.37, said, "It's definitely fun to be around so many great competitors."
The third time was a charm in the 13-14 boys 4 km run as Erik Gonzalez of the Socal Road Runners took first with his time of 12:59.54. Gonzales finished seventh in his first appearance at this event before finishing 12th last year.
"I think I had a decent start," he said. "I had my teammates with me, and I felt good about it. The second mile, I decided to just go for it and take the finish."
Gabriel Fendel of the Cascade Striders took second in 13:06.8 while Devin Paredes of Cougar Track Club finished in 13:08.67.
In the 15-16 girls division, Lauren Jacob of the Buffalo Chips Running Club took the first 5 km crown, finishing in 18:20.76. Amanda Gehrich, running unattached, followed in 3:42.6 and Julia Wood of Richmond crossed in 18:53 for third.
Phillip Rocha from O'Brien's Army was the top finisher in the 15-16 boys race with his time of 15:47.36. Jacob Ogden of the South Orange County Wildcats came in at 16:02.73 and Jarit Perkins of Evansville rounded out the top in 16:04.74.
Buffalo Chips runner Karlie Garcia took her lead and never looked back to finish in 17.36.09, nearly a minute ahead of her competitors. Veronica Yamane, who ran unattached, finished in 18:38.04, and Francesca Loayza - also of the Buffalo Chips - was the third place finisher with her 19:10.51.
Yamane, competing for a third time, said, "For the first part I was trailing, I thought maybe I could go a little faster. After that, I was just focussing on the girl ahead of me."
In the final race, Estevan De La Rosa of O'Brien's Army crossed in 15:31.68 for first place. Teammate Jarrick Wenslow was next in 16:04.43. Alex Conn of Hays Strider was third with his time of 16:08.43.
Two-time Olympic silver medalist Leo Manzano will present awards to top race and team finishers at Sea World's Ski Stadium Saturday evening.
For full results, click here.
Christa Mann


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Tuesday, August 17, 2010
Modif Kawasaki Ninja 250 RPosted by eightq at 1:47 AM
|Modif Kawasaki Ninja 250 R
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|Modif Kawasaki Ninja 250 R
|Modif Kawasaki Ninja 250 R
|Modif Kawasaki Ninja 250 R
Front tire: Battlax 120/70-17
Rear tire: Battlax 160/70-17
Rim: Fire Blade 400
Upside down: Yamaha R6 2008
Footstep: Yoshimura
Exhaust: Yoshimura
X-Bike: 0815-1000-742
Labels: KAWASAKI
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day 752:
do you have your collection of spots that you like to visit when you return to a favourite city? although i love to experience new things, there are some places that make me feel like i'm back in town....like this place in Cape Town {see day 437} and dragon-i in Hong Kong.
it's a nightclub by....well....night.....and a popular (and amazing value) dim sum restaurant by day. so, you get to lunch under fairly dramatic lighting for your dumplings and emerge to a bustling Central Hong Kong. it fits in perfectly with a city that bridges East with West, decadence with simplicity and contemporary modern living with strong tradition and beliefs.


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Aston Martin Works – OMI
Newport Pagnell has been Aston Martin's spiritual home since 1955. It's factory there wasn't exactly an ideal site, with buildings on both sides of a busy main road, but logistical issues didn't stop Aston building some of its greatest cars there.
Aston opened a brand-new, state-of-the-art facility at Gaydon in 2003, but Newport Pagnell continued turning out the Vanquish until it was discontinued in 2007.
The site has since become the home of Aston Martin Works, the service, restoration and heritage division, and a Mecca for Aston fans from across the world.
Tim and Jim made the pilgrimage to see what goes on at Newport Pagnell and to chat to the people who keep Aston Martin's heritage alive.


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Alfajores - a holiday baking idea from The Foodie Handbook
Here's another recipe from my new book I'd like to share, and this is just the perfect time for it. Aren't we all thinking about holiday baking these days? Ok, if you're in Northern California you must be thinking freezing weather too - you've heard all the complaints on twitter I'm sure - so, what better than baking for an excuse to turn on your oven and warm up the house?
It will also be fun to do something slightly different than the usual sugar or gingerbread cookies, don't you agree? I highly recommend these Alfajores, two buttery, crumbly cookies hugging the sweet dulce de leche (a sort of caramelized milk jam), your friends and relative will appreciate the novelty. You may have to teach them how to say the name, al-fa-ho-res, but once they bite into these addictively delicious cookies, they won't mind one bit.
Don't let the fact that these cookies are so deliciously delicate - they seem to crumble under too intense a gaze - deter you. While being made, the dough is so easy to work with it feels like Play-doh.
Alfajores cookies250g cornstarch (2 cups – see method below*)
200g all purpose flour (1 1/2 cup)
1/2 tsp salt
1/2 tsp baking soda
2 tsp baking powder
200g, 7oz (14tbsp) butter at room temperature
75g sugar (1/3 cup )
3 egg yolks
1tbsp cognac
1 cup Dulce de Leche (see below**)
*If you don't have a kitchen scale, this recipe should convince you to go get one. Cornstarch is quite difficult to measure in volume, so the measurement here is by weight instead. If you don't have a kitchen scale and don't want to buy one (whatever!) you can sift the cornstarch directly onto your measuring cup. Line a pasty board or your countertop with a large piece of parchment paper, place a one cup dry-measure in the middle of it. Pour cornstarch into a sifter or a large strainer and sift it directly over the measuring cup. Continue sifting until you fill the cup with sifted cornstarch. You can tap the cup gently just to let the cornstarch settle into the cup, but do it very gently as you don't want to pack cornstarch tightly into it. Level the top with the back of a knife. Pour the measured cornstarch into another bowl, pour the excess cornstarch on the paper back into the box, then repeat the process to measure the second cup. Measuring this way you should get about 250g from two cups, precisely what you need in this recipe.Preheat the oven to 350F (175C).
Sift flour, cornstarch, salt, baking powder and baking soda together. Set aside.
In the bowl of a stand mixer, beat the butter, sugar, and yolks on high speed until they are well incorporated, add cognac and beat until combined. Reduce the speed to low, add the dry ingredients a bit at a time until well incorporated. Empty the bowl onto a dry board and knead the mixture just until it comes together into dough. Divide the dough into two balls. At this point you can wrap each with plastic and store in the fridge for up to a day until you're ready to use them.
If the dough has been refrigerated, let it sit out at room temperature for a short time to warm up a bit. Then, on a lightly-floured board, roll each ball of dough until it is 1/4 inch or 5mm thick. Use a 3inch or 6-7cm fluted cookie cutter to cut 20-25 cookies from each half of the dough. You can gather the excess dough together and roll it again. (This dough is very forgiving.) Place the cut cookies onto two large cookie sheets, leaving just half an inch or 1cm between them - they only expand a tiny bit while baking.
Bake the cookies for 15-20 minutes, switching the baking sheets about halfway through. The cookies should change the color only slightly. Remove from the oven immediately, let stand on the cookie sheet for about two minutes. Then, handling them gently, transfer them onto a rack to cool.
To finish the cookies, fill a pastry bag with the dulce de leche and pipe about 1 tbsp on top of half the cookies. If you don't have a pastry bag, just spread the dulce de leche onto the cookies with a butter knife. Be careful, these cookies are very delicate. Top the filled cookies with the other half, making little cookie sandwiches, pressing down a little so the filling is spread evenly. Sift a bit of powdered sugar on top just before serving. You can also roll the side of the cookies over coconut flakes to make them even more delicious (and authentic.)
**Dulce de Leche
1 14oz or 400g can of sweetened condensed milk
1 vanilla pod (if you want to splurge, or just a teaspoon of vanilla extract (added at the end)
Preheat the oven to 425F
Open the can of condensed milk and pour it into a medium-sized baking pan. (I use a glass pyrex pie plate for this.) Cut the vanilla pod in half lengthwise (if using) and scrape out the seeds. Add them to the condensed milk and mix well. You can even throw in the pod as well, just remove them after the cooking. Cover the baking pan with aluminum foil.
Place the baking pan on top of a larger pan with high sides. Add water to the larger pan until it comes halfway up to the side of the small pan. Place it in the oven and bake for about one hour. Check it every so often to make sure there's still water in the pan, fill it if necessary.
Remove the pan from the oven, take out the vanilla pod (or add vanilla extract if using) whisk until the texture is smooth. Let it cool to room temperature before using.