eSource and Direct Data Entry – 2 New Programs in Oncology
Target Health is pleased to announce that it has received 2 new programs in oncology that will utilize Target e*CTR® (eClinical Trial Record) fully integrated with Target e*CRF®. The programs will be at major oncology centers in the US.
Target e*CTR allows the clinical study sites to perform direct data entry into any EDC system. This patented process generates a read-only, human readable electronic document, which can be designated as the primary source data (eSource). These records, maintained in a secure, read-only trusted 3rd party environment, are available to the clinical study sites, monitors and regulatory agencies in a human readable format, and carry a full audit-trail.
These 2 new studies under 2 INDs add to the 11 studies under 6 INDs which have utilized Target e*CTR. Bottom line, around 3% of forms are queried and about 1% of forms are being changed. We can assure our readers that the changes made to the database do not affect patient safety, data integrity, data quality and trial outcomes. What is happening is that data are entered and reviewed in “real time,” and when the study subject leaves the clinic, there is virtually no more work to do till the next visit.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website.
Immunity: A Secret to Making Macrophages
Blood progenitor cells differentiating in culture. The brightness of green indicates the amount of the regulatory protein PU.1 present. These images are from a time-lapse movie taken over the course of differentiation. (Credit: Hao Yuan Kueh, Michael Elowitz and Ellen Rothenberg/Caltech)
Biologists at the California Institute of Technology (Caltech) have worked out the details of a mechanism that leads undifferentiated blood 1) ___ cells to become macrophages — immune cells that attack bacteria and other foreign pathogens. The process involves an unexpected cycle in which cell division slows, leading to an increased accumulation of a particular regulatory protein that in turn slows cell division further. The finding provides new insight into how stem cells are guided to generate one 2) ___ type as opposed to another.
Previous research has shown that different levels of a key regulatory protein called PU.1, which is involved in the new cycle, are important for the production of at least four different kinds of differentiated 3) ___ cells. For example, levels of PU.1 need to increase in order for macrophages to form, but must decrease during the development of another type of white blood cell known as the B cell. Precisely how such PU.1-level changes occur and are maintained in the cells has been unclear. But by observing differentiation in both macrophages and B cells, the Caltech team discovered something unusual in the feedback loop that produces macrophages. Their findings appear in the current July 2013 issue of Science Express. “Our results explain how blood stem cells and related progenitor cells can differentiate into 4) ___ and slow down their cell cycle, coordinating these two processes at the same time,” says lead author Hao Yuan Kueh, a postdoctoral scholar at Caltech who works with biologists Michael Elowitz and Ellen Rothenberg, who were both principal investigators on the study. “We are excited about this because it means other systems could also use this mechanism to coordinate cell proliferation with differentiation.”
In the study, the researchers captured movies of blood stem cells taken from transgenic mice. The cells expressed a green fluorescent 5) ___ that serves as an indicator of PU.1 levels in the cell: the brighter the cells appeared in the movies, the more PU.1 was present. By measuring PU.1 levels over time using this indicator, the scientists were able to monitor changes in the rate of PU.1’s synthesis.
PU.1 can work through a positive feedback loop, binding to its own DNA regulatory sequence to stimulate its own production in a self-reinforcing manner. This type of loop is thought to be a general mechanism that allows a stem cell to switch into a differentiated state. In the case of PU.1, the process cranks up to produce macrophages, for example, and turns down to produce B cells.
And, indeed, when the researchers looked at B cell development, they saw what they expected: developing B cells decreased PU.1 levels by putting the brakes on the production of the protein. The surprise came when they observed macrophages. Although the amount of PU.1 in the cells 6) ___ when the stem cells became macrophages, the researchers saw no change in the rate of PU.1 synthesis.
So where was the increase coming from? Upon investigation, the researchers observed that cells increased their PU.1 levels simply by slowing down their rate of division. With fewer cells being produced as the rate of PU.1 production marched steadily on, higher levels of the PU.1 protein were able to accumulate in the cells. Indeed, by slowing down the cell cycle, the researchers found that they could raise PU.1 levels enough to prompt the generation of macrophages. This result suggested that a different type of positive feedback 7) ___ might be responsible for the decisive final increase in PU.1 levels during macrophage differentiation. “This work shows the amazing power of movies of individual cells in deciphering the dynamics of gene circuits,” says Elowitz, who is a professor of biology and bioengineering at Caltech and an investigator with the Howard Hughes Medical Institute. “Just by following how the amount of PU.1 protein changed over time in a single cell, one can see directly that cells use a very different kind of feedback architecture than we usually associate with cellular differentiation.”
To test what kind of positive feedback loop might control these events, the researchers forced cells to express extra PU.1, and measured its effect on the cells’ own PU.1. They found that the extra PU.1 did not boost the cell’s own PU.1 synthesis rate any further, but instead slowed the rate of cell division, causing PU.1 to accumulate to higher 8) ___ in the cells — an effect that slowed the cell cycle further. “The key to this mechanism is that PU.1 is a very stable protein,” says Rothenberg, the Albert Billings Ruddock Professor of Biology at Caltech. “Its central role in blood cell development has come from the fact that it collaborates with different regulatory protein partners to guide stem cells to make different cell types. We’ve known for some time that the exact ratios between PU.1 and its partners are important in these decisions, but it has been hard to see how the cells can manage to control the 9) ___ between so many of these different regulators with such precision. The beauty of this mechanism is that this ratio can be controlled simply by altering cell-cycle length. This shows us a new tool that factors like PU.1 and its collaborators can use to guide stem cells into precise developmental paths.”
The team also used mathematical modeling to test the properties of a feedback loop that relies on the length of the cell cycle. They were able to show that a system that incorporated both the new loop and the PU.1-production feedback loop was able to account for three distinct levels of PU.1 — one corresponding to B cells, one to progenitor cells, and one to macrophages. “That was a proof-of-principle that this type of architecture can work,” Kueh says. “The modeling will also help us to generate 10) ___ for future studies.”
In addition to Kueh, Elowitz, and Rothenberg, the paper, titled “Positive feedback between PU.1 and the cell cycle controls myeloid differentiation,” is also coauthored by Ameya Champhekar, a postdoctoral scholar at Caltech, and Stephen Nutt, head of the Division of Molecular Immunology at the Walter and Eliza Hall Institute of Medical Research in Parkville, Victoria, Australia. The work was supported by a CRI Irvington Postdoctoral Fellowship, an Australian Research Council Future Fellowship, the Victorian State Government Operational Infrastructure Support, the National Health and Medical Research Council of Australia, the National Institutes of Health, the Albert Billings Ruddock Professorship, the Al Sherman Foundation, and the Louis A. Garfinkle Memorial Laboratory Fund. Additional source: ScienceDaily.com
ANSWERS: 1) stem; 2) cell; 3) blood; 4) macrophages; 5) protein; 6) increased; 7) loop; 8) levels; 9) balance; 10) predictions
Vivien T. Thomas (1910-1985)
Vivien T. Thomas, 1969
Vivien Theodore Thomas (August 29, 1910 – November 26, 1985) was an African-American surgical technician who developed the procedures used to treat blue baby syndrome in the 1940s. He was an assistant to surgeon Alfred Blalock in Blalock’s experimental animal laboratory at Vanderbilt University in Nashville, Tennessee, and later at the Johns Hopkins University in Baltimore, Maryland. Without any education past high school, Thomas rose above poverty and racism to become a cardiac surgery pioneer and a teacher of operative techniques to many of the country’s most prominent surgeons. Vivien Thomas was the first African American without a doctorate to perform open heart surgery in the United States.
Thomas was born in New Iberia, Louisiana. The grandson of a slave, he attended Pearl High School in Nashville in the 1920s. Thomas had hoped to attend college and become a doctor, but the Great Depression derailed his plans. In the wake of the stock market crash in October, Thomas put his educational plans on hold, and, through a friend, in February 1930 secured a job as surgical research technician with Dr. Alfred Blalock at Vanderbilt University. On his first day of work, Thomas assisted Blalock with a surgical experiment on a dog. At the end of Thomas’s first day, Blalock told Thomas they would do another experiment the next morning. Blalock told Thomas to “come in and put the animal to sleep and get it set up”. Within a few weeks, Thomas was starting surgery on his own. Thomas was classified and paid as a janitor, despite the fact that by the mid-1930s, he was doing the work of a postdoctoral researcher in the lab.
Thomas and Blalock did groundbreaking research into the causes of hemorrhagic and traumatic shock. This work later evolved into research on Crush syndrome and saved the lives of thousands of soldiers on the battlefields of World War II. In hundreds of flawlessly executed experiments, the two disproved traditional theories which held that shock was caused by toxins in the blood. Blalock, a highly original scientific thinker, had theorized that shock resulted from fluid loss outside the vascular bed and that the condition could be effectively treated by fluid replacement. Assisted by Thomas, he was able to provide incontrovertible proof of this theory, and in so doing, he gained wide recognition in the medical community by the mid-1930s. At this same time, Blalock and Thomas began experimental work in vascular and cardiac surgery, defying medical taboos against operating upon the heart. It was this work that laid the foundation for the revolutionary lifesaving surgery they were to perform at Johns Hopkins a decade later.
By 1940, the work Blalock had done with Thomas placed him at the forefront of American surgery, and when he was offered the position of Chief of Surgery at his alma mater Johns Hopkins in 1941, he requested that Thomas accompany him. Thomas arrived in Baltimore with his family in June of that year, confronting a severe housing shortage and a level of racism worse than they had endured in Nashville. Hopkins, like the rest of Baltimore, was rigidly segregated, and the only black employees at the institution were janitors. When Thomas walked the halls in his white lab coat, many heads turned. In 1943, while pursuing his shock research, Blalock was approached by renowned pediatric cardiologist Dr. Helen Taussig, who was seeking a surgical solution to a complex and fatal four-part heart anomaly called Tetralogy of Fallot (also known as blue baby syndrome, although other cardiac anomalies produce blueness, or cyanosis). In infants born with this defect, blood is shunted past the lungs, thus creating oxygen deprivation and a blue pallor. Having treated many such patients in her work in Hopkins’s Harriet Lane Home, Taussig was desperate to find a surgical cure. According to the accounts in Thomas’s 1985 autobiography and in a 1967 interview with medical historian Peter Olch, Taussig suggested only that it might be possible to “reconnect the pipes” in some way to increase the level of blood flow to the lungs but did not suggest how this could be accomplished. Blalock and Thomas realized immediately that the answer lay in a procedure they had perfected for a different purpose in their Vanderbilt work, involving the anastomosis, or joining, of the subclavian to the pulmonary artery, which had the effect of increasing blood flow to the lungs.
Thomas was charged with the task of first creating a blue baby-like condition in a dog, and then correcting the condition by means of the pulmonary-to-subclavian anastomosis. Among the dogs on whom Thomas operated was one named Anna, who became the first long-term survivor of the operation and the only animal to have her portrait hung on the walls of Johns Hopkins. In nearly two years of laboratory work, involving some 200 dogs, Thomas was ultimately able to replicate only two of the four cardiac anomalies involved in Tetralogy of Fallot. He did demonstrate that the corrective procedure was not lethal, thus persuading Blalock that the operation could be safely attempted on a human patient. Even though Thomas knew he was not allowed to operate on patients at that time, he still followed Blalock’s rules and assisted him during surgery.
On November 29, 1944, the procedure was first tried on an eighteen-month-old infant named Eileen Saxon. The blue baby syndrome had made her lips and fingers turn blue, with the rest of her skin having a very faint blue tinge. She could only take a few steps before beginning to breathe heavily. Because no instruments for cardiac surgery then existed, Thomas adapted the needles and clamps for the procedure from those in use in the animal lab. During the surgery itself, at Blalock’s request, Thomas stood on a step stool at Blalock’s shoulder and coached him step by step through the procedure, Thomas having performed the operation hundreds of times on a dog, Blalock only once, as Thomas’ assistant. The surgery was not completely successful, though it did prolong the infant’s life for several more months. Blalock and his team operated again on an 11-year-old girl, this time with complete success, and the patient was able to leave the hospital three weeks after the surgery. Next, they operated upon a six-year-old boy, who dramatically regained his color at the end of the surgery. The three cases formed the basis for the article that was published in the May 1945 issue of the Journal of the American Medical Association, giving credit to Blalock and Taussig for the procedure. Thomas received no mention.
News of this groundbreaking story was circulated around the world by the Associated Press. Newsreels touted the event, greatly enhancing the status of Johns Hopkins and solidifying the reputation of Blalock, who had been regarded as a maverick up until that point by some in the Hopkins old guard. Thomas’ contribution remained unacknowledged, both by Blalock and by Hopkins. Within a year, the operation known as the Blalock-Taussig shunt had been performed on more than 200 patients at Hopkins, with parents bringing their suffering children from thousands of miles away.
Thomas’s surgical techniques included one he developed in 1946 for improving circulation in patients whose great vessels (the aorta and the pulmonary artery) were transposed. A complex operation called an atrial septectomy, the procedure was executed so flawlessly by Thomas that Blalock, upon examining the nearly undetectable suture line, was prompted to remark, “Vivien, this looks like something the Lord made.” To the host of young surgeons Thomas trained during the 1940s, he became a figure of legend, the model of a dexterous and efficient cutting surgeon. “Even if you’d never seen surgery before, you could do it because Vivien made it look so simple,” the renowned surgeon Denton Cooley told Washingtonian magazine in 1989. “There wasn’t a false move, not a wasted motion, when he operated.” Surgeons like Cooley, along with Alex Haller, Frank Spencer, Rowena Spencer, and others credited Thomas with teaching them the surgical technique that placed them at the forefront of medicine in the United States.
Despite the deep respect Thomas was accorded by these surgeons and by the many black lab technicians he trained at Hopkins, he was not well paid. He sometimes resorted to working as a bartender, often at Blalock’s parties. This led to the peculiar circumstance of his serving drinks to people he had been teaching earlier in the day. Eventually, after negotiations on his behalf by Blalock, he became the highest paid technician at Johns Hopkins by 1946, and by far the highest paid African-American on the institution’s rolls. Although Thomas never wrote or spoke publicly about his ongoing desire to return to college and obtain a medical degree, his widow, the late Clara Flanders Thomas, revealed in a 1987 interview with Washingtonian writer Katie McCabe that her husband had clung to the possibility of further education throughout the Blue Baby period and had only abandoned the idea with great reluctance. Mrs. Thomas stated that in 1947, Thomas had investigated the possibility of enrolling in college and pursuing his dream of becoming a doctor, but had been deterred by the inflexibility of Morgan State University, which refused to grant him credit for life experience and insisted that he fulfill the standard freshman requirements. Realizing that he would be 50 years old by the time he completed college and medical school, Thomas decided to give up the idea of further education.
Blalock’s approach to the issue of Thomas’s race was complicated and contradictory throughout their 34-year partnership. On the one hand, he defended his choice of Thomas to his superiors at Vanderbilt and to Hopkins colleagues, and he insisted that Thomas accompany him in the operating room during the first series of tetralogy operations. On the other hand, there were limits to his tolerance, especially when it came to issues of pay, academic acknowledgment, and his social interaction outside of work. After Blalock’s death from cancer in 1964 at the age of 65, Thomas stayed at Hopkins for 15 more years. In his role as director of Surgical Research Laboratories, he mentored a number of African-American lab technicians as well as Hopkins’ first black cardiac resident, Dr. Levi Watkins, Jr., whom Thomas assisted with his groundbreaking work in the use of the Automatic Implantable Defibrillator.
Racial bias dies-hard, and progress is slow; however, Vivien Thomas’ nephew, Koco Eaton, graduated from the Johns Hopkins School of Medicine, trained by many of the same physicians his uncle had trained. Eaton trained in orthopedics and is now the team doctor for the Tampa Bay Rays.
In 1968, the surgeons Thomas trained – who had then become chiefs of surgical departments throughout America – commissioned the painting of his portrait (by Bob Gee, oil on canvas, 1969, The Johns Hopkins Alan Mason Chesney Medical Archives) and arranged to have it hung next to Blalock’s in the lobby of the Alfred Blalock Clinical Sciences Building. This is the portrait, you see at the beginning of this piece. In 1976, Johns Hopkins University presented Thomas with an honorary doctorate. However, because of certain restrictions, he received an Honorary Doctor of Laws, rather than a medical doctorate, but it did allow the staff and students of Johns Hopkins Hospital and Johns Hopkins School of Medicine to call him doctor. Thomas was also appointed to the faculty of School of Medicine as Instructor of Surgery.
In July 2005, Johns Hopkins School of Medicine began the practice of splitting incoming first year students into four colleges, each named for famous Hopkins faculty members that had major impacts on the history of medicine. Thomas was chosen as one of the four, along with Helen Taussig, Florence Sabin, and Daniel Nathans.
Following his retirement in 1979, Thomas began work on an autobiography, Partners of the Heart: Vivien Thomas and his Work with Alfred Blalock, ISBN 0-8122-1634-2. He died on November 26, 1985, of pancreatic cancer, at age 75, and the book was published just days later. Having learned about Thomas on the day of his death, Washingtonian writer Katie McCabe brought his story to public attention for the first time in a 1989 article entitled “Like Something the Lord Made”, which won the 1990 National Magazine Award for Feature Writing and inspired filmmaker Andrea Kalin to make the PBS documentary “Partners of the Heart,” which was broadcast in 2003 on PBS’s American Experience and won the Organization of American Historians’ Erik Barnouw Award for Best History Documentary in 2004. Especially for those interested in history of medicine, this is a beautiful, thoughtful and compelling film, worth adding to your DVD library. McCabe’s article, brought to Hollywood by Washington, D.C. dentist Irving Sorkin, formed the basis for the Emmy and Peabody Award-winning 2004 HBO film: Something the Lord Made.
Thomas’s legacy as an educator and scientist continued with the institution of the Vivien Thomas Young Investigator Awards, given by the Council on Cardiovascular Surgery and Anesthesiology beginning in 1996. In 1993, the Congressional Black Caucus Foundation instituted the Vivien Thomas Scholarship for Medical Science and Research sponsored by GlaxoSmithKline. In Fall 2004, the Baltimore City Public School System opened the Vivien T. Thomas Medical Arts Academy, and on January 29, 2008, MedStar Health unveiled the first “Rx for Success” program at the Academy, joining the conventional curriculum with specialized coursework geared to the health care professions. In the halls of the school hangs a replica of Thomas’s portrait commissioned by his surgeon-trainees in 1968. The Journal of Surgical Case Reports (JSCR) announced in January 2010 that their annual prizes for the best case report written by a doctor and best case report written by a medical student would be named after Thomas.
Rapid Test Allows For Earlier Diagnosis of TB in Children
Preliminary diagnosis of TB is often made by collecting a sample of lung secretions and examining the sample under a microscope to see if it contains the bacteria that cause TB. A sample is also sent to a laboratory so the bacteria can be cultured and identified. It may take as long as six weeks for the culture test to show a positive result. Because, children have lower levels of infectious bacteria than do adults, it is more difficult to detect the TB bacteria under a microscope and to grow it in a culture. For this reason, accurately diagnosing TB in children has been difficult.
According to the results of a study in South Africa published in The Lancet Global Health (2013; 1:e97-e104) and supported by the NIH, a new test for diagnosing TB in children detects roughly two-thirds of cases identified by the current culture test, but in a fraction of the time. The test, known as Xpert MTB/RIF, also detected five times the number of cases identified by examining specimens under the microscope, a preliminary method for diagnosis that is often performed as an initial test, but which must be verified by the culture test.
Xpert MTB/RIF results from respiratory secretions were ready in 24 hours, on average, compared with an average of more than two weeks for the culture test used in the study. Previous studies have shown that Xpert MTB/RIF is effective for diagnosing TB in adults and in children with pronounced symptoms of TB who have been admitted to a hospital. Diagnosing TB in children is more difficult than diagnosing it in adults, because children tend to have much lower levels of the TB bacteria than do adults. The results of the current study indicated that the ease and speed of diagnosis would be useful for children seen in clinics in resource-limited countries, which often lack the resources for traditional testing that are available in hospitals. The test also was able to identify children with drug resistant TB. In addition, the authors found that Xpert can readily determine when treatment for tuberculosis is not appropriate. Among children who did not in fact have TB, the results of the Xpert test came back negative for TB with 99% accuracy. The Xpert MTB/RIF test also detects TB strains that are resistant to the drug rifampicin, allowing physicians to more accurately prescribe an appropriate treatment. This is particularly important in areas where drug-resistant TB is common, such as South Africa.
The study collected almost 1,500 samples from nearly 400 children who went to a primary care clinic with symptoms of TB. Collecting the samples — secretions from the lungs, the nasal passages or both — requires special equipment and trained clinical staff. The authors compared the results from the Xpert MTB/RIF test, examination of samples under a microscope, and from growing the tuberculosis bacteria in laboratory cultures. Bacterial culture is the most accurate method for diagnosing TB. Of the 30 TB cases detected by culture, 19 (63%) were positive by the Xpert MTB/RIF test on lung or nasal samples, while examining the samples under the microscope turned up only four cases (13%). Adding a second test (of a second lung or nasal passage sample) improved the detection rate for both culture and Xpert MTB/RIF
In some cases, the authors started TB treatment for children they suspected had TB, based on their symptoms. Xpert MTB/RIF identified seven children who had clinical symptoms of TB and responded well to treatment, but whose TB had not been detected by the TB culture test. This might occur when a child is sick with TB, but the bacteria are at especially low levels, or because a sample did not contain enough of the bacteria present in the child’s body to appear when cultured. The total number of cases detected by culture (30 cases) and by XpertMTB/RIF (26 cases) was similar.
Silky Brain Implants May Help Stop Spread of Epilepsy
The epilepsies are a group of neurological disorders associated with recurring seizures that tend to become more frequent and severe over time. Adenosine decreases neuronal excitability and helps stop seizures. Earlier studies have suggested abnormally low levels of adenosine may be linked to epilepsy and that novel silk-based polymers, engineered to release the anticonvulsant adenosine, might prove to be efficacious
According to a new study published in the Journal of Clinical Investigation (July 25, 2013), silk implants placed in the brain of laboratory animals and designed to release a specific chemical, adenosine, may help stop the progression of epilepsy. According to the authors, adenosine’s beneficial effects are due to epigenetic modifications (chemical reactions that change the way genes are turned on or off without altering the DNA code, the letters that make up our genetic background). Specifically, these changes happen when a molecule known as a methyl group blocks a portion of DNA, affecting which genes are accessible and can be turned on. If methyl groups have been taken away (demethylated), genes are more likely to turn on.
The results provided evidence that changing adenosine levels affects DNA methylation in the brain. Specifically, greater amounts of adenosine were associated with lower levels of DNA methylation. The authors also demonstrated that rats induced to develop epilepsy have higher levels of methylated DNA. Of particular note, epileptic rat brains that had received the adenosine-releasing silk implants exhibited DNA methylation levels close to brains of normal rats and this significantly lessened the worsening of the epilepsy over time.
One mechanism involved in a specific type of epilepsy is an increase in mossy fiber sprouting — the formation of new excitatory circuits in the part of the brain where seizures commonly originate. At the end of the experiment, animals that had been treated with the adenosine — releasing silk implant showed less sprouting than animals that were not given the drug. Based on the findings that 10 days of adenosine delivery prevented the sprouting of mossy fibers for at least three months in rats, the authors predict that the benefits of the adenosine therapy may extend even longer. However, the authors added, this assumption needs to be validated in long-term experiments that go beyond three months.
As part of the study design, the rats did not receive the implants until they had experienced a number of seizures. The authors noted that many studies investigating anti-epileptic drugs often test the treatments too early. According to the authors, if the therapy interferes with the trigger for epilepsy development then the trigger is weakened and subsequent epilepsy is less severe. However, this is not necessarily indicative of a stop in the progression of the disease. To support this hypothesis, the study found that the adenosine-releasing silk did not completely abolish seizures in their animal model but reduced them four-fold.
The findings show that the implants are safe to use in rats and suggest that they may one day be used in the clinic as the adenosine-releasing silk is a biodegradable implant. The release of adenosine occurs for 10 days and then the silk will completely dissolve. This is an ideal set-up for a transient preventative treatment. Clinical applications could be the prevention of epilepsy following head trauma or the prevention of seizures that often – in about 50% of patients – follow conventional epilepsy surgery. In this case, adenosine-releasing silk might be placed into the resection cavity in order to prevent future seizures.
However, before the silk implants are ready for their close-up, future studies will need to determine their optimal use and safety in humans. And there is a need to look into the efficacy of different doses of adenosine, the duration of adenosine release, and various time points of intervention. In addition, future studies also need to demonstrate how long the effects of the adenosine-releasing silk implant will last.
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area
Despite decades of work, tobacco use continues to be the leading cause of preventable death and disease in the United States. About 30% of all adult smokers and more than 40% of all youth smokers report smoking menthol cigarettes.
The FDA has issued an Advance Notice of Proposed Rulemaking (ANPRM) seeking additional information to help the agency make informed decisions about menthol in cigarettes. The agency is issuing the ANPRM to obtain additional information related to potential regulatory options it might consider, such as establishing tobacco product standards, among others. The ANPRM will be available for public comment for 60 days. The FDA will consider all comments, data, research, and other information submitted to the docket to determine what, if any, regulatory action with respect to menthol in cigarettes is appropriate. If the FDA decides to issue a rule, the first step in that process would be a Notice of Proposed Rulemaking, which would give the public an opportunity to weigh in on the specifics of the proposed rule.
The FDA is also making available for public comment relevant scientific information, including the FDA’s independent Preliminary Scientific Evaluation of the Possible Public Health Effects of Menthol Versus Nonmenthol Cigarettes. The preliminary evaluation addresses the association between menthol cigarettes and various outcomes, including initiation, addiction, and cessation.
In addition, the FDA plans to support new research on the differences between menthol and non-menthol cigarettes as they relate to menthol’s likely impact on smoking cessation and attempts to quit, as well as assessing the levels of menthol in cigarette brands and sub-brands. The FDA is funding three menthol-related studies; one to look at whether genetic differences in taste perceptions explain why certain racial and ethnic populations are more likely to use menthol cigarettes; the second to compare exposure to smoke-related toxins and carcinogens from menthol and nonmenthol cigarettes; and a third to examine the effects of menthol and nonmenthol compounds in various tobacco products on both tobacco addiction and toxicants of tobacco smoke.
Finally, the FDA is developing a youth education campaign focused on preventing and reducing tobacco use, including menthol cigarettes.
Fresh Peach Wine Punch (chilled)
1 bottle white wine (750 mls) like Sauvignon blanc, Asti (sparkling) wine or Zinfandel
1/2 cup peach brandy
1 cup triple sec
1 cup fresh orange juice
1 cup pineapple juice
2 ounces agave
2 fresh peaches, skinned and pureed in food processer
2 fresh peaches, skinned and cut into bite-size pieces
Fresh pineapple pieces (optional: you decide how many)
Club soda or seltzer
Garnishes for edge of glass: segment fresh peach (skinned or not), thin slice of fresh orange, tiny sprig of mint
Place all ingredients in a pitcher and stir to mix.
1. Refrigerate at least 8 hours or up to 48 hours.
2. To serve you can add club soda to the entire pitcher, to give the punch a “fizz”. Or, you can pour 1/2 glass with club soda, filled with plenty of ice, and then pour the punch. Serve with a segment of fresh peach or a slice of fresh orange, for color.
3. For zero alcohol punch, simply substitute sparkling white grape juice for the ingredients with alcohol. For the peach puree, use 4 fresh peaches instead of two. Also, you might prefer to use ginger ale instead of club soda.
Very refreshing. I recommend keeping extra wine on hand, as guests will want more and more. Chilling this for at least 8 hours is good, so you might as well chill overnight. The reason to chill your punch or sangria overnight, is to let the flavors mix nicely, to taste better.
Because peaches, now in season, are absolutely juicy and delicious, it’s preferable to use segments of these for the side of each glass. Their juice might drip a bit more than a slice of orange, but so what – the peaches this year are so yummy, no one will mind. We’re eating a luscious juicy peach each day this summer, because the flavor, this year, is outstanding!
Nibble on Kale Patties – use the recipe from a few weeks back.
Based on all the recipes for punch or sangria, in this section, use your creativity and make up your own recipe, from what you read. Because the fresh peaches are extra delicious this summer, start with this ingredient, and you’re sure to have a big success for your family and guests. Don’t hesitate to combine fresh peaches with icy champagne.
The beauty of the basic Sangria recipe is that it’s as delicious as it is easy, and it only gets better as you spice it up with your own additions! It’s hard to add the “wrong” ingredient here, think favorite fruits, spice and liquors. Chill and enjoy.
1 Bottle of red wine (Cabernet Sauvignon, Merlot, Rioja reds, Zinfandel, Shiraz)
1 Lemon cut into wedges
1 Orange cut into wedges
1 cup fresh strawberries, cut in half
1 fresh juicy peach, cut into pieces (you decide about the skin)
2 Tbsp sugar or sugar substitute or agave
1 Shot brandy (like peach brandy)
2 Cups ginger ale or club soda
Pour wine in the pitcher and squeeze the juice wedges from the lemon and orange into the wine. Toss in the fruit wedges (leaving out seeds if possible), plus the cut-up pieces of fresh fruit. Add agave and brandy. Chill overnight. Add ginger ale or club soda just before serving.
If you’d like to serve right away, use chilled red wine and serve over lots of ice.
Addition ideas: handful of fresh blueberries, raspberries, kiwi, a shot or two of gin, brandy or rum, a cup of ginger ale, citrus soda pop or lime juice. If you want a zero alcohol drink, substitute all of the alcohol in this recipe with sparkling grape juice, with some gingerale and a few splashes of fresh orange juice
Red Summer Sangria
Red Summer Sangria
1 (750 ml) bottle of MARTINI Bianco vermouth
8 ounces apple juice
4 ounces cranberry juice
4 ounces agave
2 ounces freshly squeezed lime juice
8 ounces MARTINI Prosecco
1 apple, cubed
1 lemon, thinly sliced into wheels
1 orange, thinly sliced into wheels
Combine first five ingredients in a large pitcher, and stir in fruit. Chill until ready to serve (24 hours, if possible). Just prior to serving, stir in Prosecco. Pour over ice in tall glasses. Makes 8-10 servings.
(If not using alcohol, replace with sparkling white grape juice).
Nibble on salmon patties – use the recipe from a few weeks back.
Raspberry Asti Float
Into a punch bowl add ice cubes (or cubes only in glasses)
1 bottle MARTINI Asti sparkling wine
Scoops raspberry sorbet (you decide how much)
10 or more fresh raspberries, frozen in freezer
Pieces of fresh pineapple
By the Glass
Add sorbet to chilled champagne flute and fill with MARTINI Asti.
Garnish with raspberries. (If not using alcohol, replace with some orange juice, a touch of lime juice, flavored club soda, and lots of raspberries and pieces of fresh pineapple).
Chilled Asti Sparkling Wine For Punch: Prosecco, Rose, Asti
Nibble on cauliflower patties – use the recipe from a few months ago.
Watermelon Gin Fizz Flow
The recipe below is for four glasses. To fill a punch bowl, simple multiply the number of guests times the number of glasses they’ll consume and make that much more watermelon fizz punch.
5 cups diced watermelon, divided
6 ounces gin, divided
8 tablespoons lime juice, divided
1 1/3 cups ginger ale, divided
Lime wedges, for garnish
Mint leaves for garnish
1. Freeze 1 cup watermelon for garnish. Puree the remaining 4 cups watermelon. Strain; divide the juice among 4 ice-filled glasses.
2. Top each with 1 1/2 ounces gin, 2 tablespoons fresh lime juice and 1/3 cup ginger ale. Garnish with the frozen watermelon and lime wedges. For the non-alcoholic variation simply: Omit the gin and use sparkling grape juice or any of the multitude of non-alcoholic sparkling drinks now on the market. I’m not promoting FreshDirect, but I did get all of the drinks below, from FreshDirect; however, they’re available everywhere
10 Delicious Non-alcoholic drinks available everywhere
Key To Above Sparkling (non-alcoholic) Drinks
1 (Kombucha Wonder Drink) Sparkling Tea Essence of Lemon
2 (Sparking Ice) Peach Nectarine Sparkling Mountain Spring Water
3 (Sparkling Ice) Coconut Pineapple Sparkling Mountain Spring Water
4 (Hint) Fizz Unsweetened Sparkling Water, Watermelon
5 (Activate) Fruit Punch – Balance (Multivitamin), Nutrient Enhanced Water Beverage
6 (Adirondack) Seltzer, Mandarin Orange
7 (Poland Spring) Raspberry-Lime Flavored Sparkling
8 (Perrier) Sparkling Pink Grapefruit Mineral Water
9 (Skinny Water) Orange Cranberry Tangerine Wake Up
10 (Canada Dry) Naturally Flavored Lemon-Lime Twist Sparkling Seltzer