Marana National Guard unit to be deployed to Afghanistan

Sunday 1 September 2013

Kabul, Sep 2 (Newswire): A Marana-based Army National Guard unit is heading to Afghanistan.

Thirty-four soldiers from Bravo Company, 1-285th Attack Reconnaissance Battalion left from Silverbell Army Heliport in support of Operation Enduring Freedom.

The unit will be deployed for a year.

The troops will spend at least two months in Fort Hood, Texas, before deploying to Afghanistan for the remainder of their tour.

The troops will join others from the battalion who are already in the country.

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Oneida's Air Force Staff Sgt. James Clarey back from Afghanistan

Oneida, Sep 2 (Newswire): There's no hype about what United States Air Force Staff Sgt. James Clarey does. He's pretty much James Bond.

The 2004 Oneida High School grad is home on leave for a week, winding down from an intense four-month tour in Afghanistan. Plastering a seven-foot-wide banner on their Main Street home's fence, his parents, Debbie and Jim Clarey, welcomed their son home. He's since spent his time with his family and wife, Monique, playing golf, visiting the New York State Fair and enjoying things he can only get here, such as wings from the Marble Hill Inn and that comfortable small-town feeling of being home.

"You never forget where you came from," Clarey said. He's soaking up the feeling of being back in a small town, something he doesn't get from his base in Las Vegas. "It's nice to be home and see familiar faces."

The enjoyment of his week's stay in his hometown is in stark contrast to the grueling four months he spent in Afghanistan. The 26-year-old spent from March to July in eastern Afghanistan. Trained as an special operative intelligence officer, it was Clarey's second trip to Afghanistan - his first tour was a few weeks long in 2006.

 
This time around, he worked with drones and MQ-1 Predator UAVs to collect intelligence in the Middle East.

In non-military terms, "it's pretty James Bondish," he admits.

But it comes at a price. As the only intel officer, he was essentially on call 24 hours a day for four months working 14- to 16-hour shifts every day. While he returned unscathed, he's had to deal with the loss of fellow servicemen. Just a few weeks after returning stateside, three special operations men he considered close friends were killed by suicide bombers.

Spending two weeks to "rest and recuperate," Clarey said he began transitioning back into his everyday life on base in Las Vegas with his wife. He returned to work for a week before coming home. He leaves next week. On a continual tour, Clarey isn't sure when and if he'll be sent overseas again but he'll continue to work using skills he developed during a year's worth of training after he enlisted, just four months after graduating high school.

He chose a profession no family member before him had. He said he knew he wanted to serve his country, see the world and benefit from the education and support the Air Force could provide. Besides Afghanistan and Las Vegas, he's served in North Carolina, Germany and other places.

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Fischler: Getting to the grass roots of the problem

Kabul, Sep 2 (Newswire): When was the last time the U.S. was an all-out, full-blown "good guy"?

Let's see ... Arab Spring? Nope, somehow we have managed to compound and enhance the negative image we have on the Arab Street. The number of young Arabs joining the ranks of anti-U.S., pro-militant Islamist groups grows every day.

Let's move back in time, to Iraq and Afghanistan. Ooops! We're not going to win any popularity contests there, either. This despite the fact that the U.S. managed to destroy the dictator Hussein in Iraq and finally assassinate Osama bin Laden.

Unfortunately, the main result of the Iraq war is that, without a dictator and/or U.S. military occupation, the country has cracked and broken into sectarian and tribal factions.

 
Iraq hovers near civil war, and on the street, it's the U.S. being blamed for the country's problems. There has been little recovery of the country's infrastructure, which simply decreases the ability of a central government to function.

Worse yet, killing bin Laden was a page out of Greek mythology: cutting one head off a many-headed Hydra. Al Qaeda is as strong as ever and currently is making inroads among the Syrian insurgents trying to oust dictator Assad.

Why is it that when a Middle Eastern, Islamic nation is "liberated" from the clutches of a dictator (whom the U.S. usually has been supporting) and is presented with the opportunity for free elections, the country moves toward militant, conservative Islam — such as in Tunisia and, most recently, in Egypt?

It's simple: Militant Islamic groups, from Hezbollah and Hamas to the Muslim Brotherhood, have learned a crucial lesson on how to win friends and influence people; it's a lesson the U.S. appears to have forgotten.

Ironically, it may well have been the U.S. that taught this lesson to militant Islamists! The example goes back in recent global history, to immediately after World War II. Indeed, this event was undoubtedly the last time the U.S. was an unmitigated "good guy."

It was called the Marshall Plan, named after then-Secretary of State George C. Marshall, a former general in the European Command of World War II. An injection of 13 billion U.S. dollars was made over four years directly into the economies of Western Europe. The aim was to rebuild and modernize European industry and infrastructure.

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Mimicking biological complexity, in a tiny particle

Islamabad, Sep 2 (Newswire): Tiny particles made of polymers hold great promise for targeted delivery of drugs and as structural scaffolds for building artificial tissues.

However, current production methods for such microparticles yield a limited array of shapes and can only be made with certain materials, restricting their usefulness.

In an advance that could broadly expand the possible applications for such particles, MIT engineers have developed a way to make microparticles of nearly any shape, using a micromold that changes shape in response to temperature. They can also precisely place drugs into different compartments of the particles, making it easier to control the timing of drug release, or arrange different cells into layers to create tissue that closely mimics the structure of natural tissues.

The new technique, described in a paper published in the Journal of the American Chemical Society, also allows researchers to create microparticles from a much more diverse range of materials, says Halil Tekin, an MIT graduate student in electrical engineering and computer science and lead author of the paper.

Currently, most drug-delivering particles and cell-encapsulating microgels are created using photolithography, which relies on ultraviolet light to transform liquid polymers into a solid gel. However, this technique can be used only with certain materials, such as polyethylene glycol (PEG), and the ultraviolet light may harm cells.

Another way to create microparticles is to fill a tiny mold with a liquid gel carrying drug molecules or cells, then cool it until it sets into the desired shape. However, this does not allow for creation of multiple layers.

The MIT research team, led by Ali Khademhosseini, associate professor in the MIT-Harvard Division of Health Sciences and Technology, and Robert Langer, the David H. Koch Institute Professor, overcame that obstacle by building micromolds out of a temperature-sensitive material that shrinks when heated.

The mold is first filled with a liquid gel that contains one kind of cell or drug. After the gel has solidified, the mold is heated so the walls surrounding the solid gel shrink, pulling away from the gel and creating extra space for a second layer to be added. The system could also be modified to incorporate additional layers, Tekin says.

"The method is quite creative," says Michael Sefton, professor at the University of Toronto Institute of Biomaterials and Biomedical Engineering, who was not involved in this project. "It offers the opportunity to make multilayer microstructures. The next step is figuring out what you can do with these two-layer structures."

So far, the researchers have created cylindrical and cubic particles, as well as long striped particles, and many other shapes should be possible, Tekin says. Their starting material was a gel made of agarose, a type of sugar.

The long striped particles would be particularly useful for engineering elongated tissues such as cardiac tissue, skeletal muscle or neural tissue. In this study, the researchers created striped particles with a first layer of fibroblasts (cells found in connective tissue), surrounded by a layer of endothelial cells, which form blood vessels.

Researchers also created cubic and cylindrical particles in which liver cells were encapsulated in the first layer, surrounded by a layer of endothelial cells. This arrangement could accurately replicate liver tissue.

Such gels could also be embedded with proteins that help the cells orient themselves in a desired structure, such as a tube that could form a capillary. The researchers are also planning to create particles that contain collagen, which constitutes much of the body's structural tissues, including cartilage.

Eventually, the researchers hope to use this technique to build large tissues and even entire organs. Such tissues could be used in the laboratory to test potential new drugs.

"If you can create 3-D tissues which are functional and really mimicking the native tissue, they are going to give the right responses to drugs," Tekin says.

This could speed up the drug discovery process and decrease the costs, because fewer animal experiments would be needed, he says.

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Five inherited genetic variants linked to the most lethal prostate cancers

Islamabad, Sep 2 (Newswire): An international team of researchers led by Fred Hutchinson Cancer Research Center has identified five inherited genetic variants that are strongly associated with aggressive, lethal prostate cancer.

The discovery ultimately could lead to the development of a simple blood test that could be given upon diagnosis to determine which men should receive aggressive treatment versus a more conservative "watchful waiting" approach.

The findings, by Janet L. Stanford, Ph.D., co-director of the Hutchinson Center's Program in Prostate Cancer Research and a member of its Public Health Sciences Division, are published in the Cancer Epidemiology, Biomarkers and Prevention.

A substantial number of men with indolent tumors -- which have a low probability of progressing to clinically significant, lethal prostate cancer -- are overtreated and, as a result, suffer side effects such as sexual impotence and urinary incontinence. In addition to its personal toll, overtreatment of indolent prostate cancer also carries a substantial economic burden, with an average of $2 billion to $3 billion spent annually in the U.S. on initial therapy alone.

"Biomarkers that could distinguish between patients with indolent versus more-aggressive tumors are urgently needed," Stanford said. "The panel of markers we've identified provides the first validated evidence that inherited genetic variants play a role in prostate cancer progression and mortality. Ultimately these markers could be used in the clinic, along with other known predictors that are used to assess tumor aggressiveness, such as a high Gleason score, to identify men with a high-risk profile."

The Hutchinson Center has filed a patent on the panel of five single-nucleotide polymorphisms, or SNPs (pronounced "snips"), which are single-letter variations within the four-letter DNA alphabet that serve as markers of genetic variation across the genome which may play a role in the development or progression of disease. "We chose to study SNPs in genes that potentially play a key role in biological pathways that may contribute to prostate cancer progression such as inflammation, steroid-hormone production and metabolism, DNA repair, circadian rhythm and vitamin D activity," Stanford said.

For the study, the researchers analyzed DNA in blood samples taken from a population-based group of 1,309 Seattle-area prostate cancer patients who were age 35 to 74 at the time of diagnosis. They evaluated 937 SNPs in 156 candidate genes and, of these, 22 SNPs emerged as being significantly associated with prostate cancer-specific mortality.

A subsequent validation study of these 22 SNPs was conducted in another population-based group of 2,875 prostate cancer patients in Sweden who were age 35 to 74 at diagnosis. Upon genotyping DNA from their blood, five of the 22 SNPs emerged as being significantly associated with death from prostate cancer. A higher proportion of patients from Sweden (17.4 percent) had died of prostate cancer relative to those from Seattle (4.6 percent) during a median follow-up period of 6.5 years, which is consistent with the higher prostate cancer mortality rate in Sweden relative to the U.S.

The five SNPs were located in or tagged, one each, to five genes that may affect prostate cancer progression:

LEPR -- The strongest marker associated with prostate cancer mortality in the study was the leptin receptor gene, which helps control tissue growth, inflammation, blood-vessel development and bone density. The latter effect makes LEPR an interesting candidate for understanding disease progression, since the primary metastatic site for prostate cancer is bone, and such metastases are predictive of fatal disease.

RNASEL -- This gene is associated with hereditary prostate cancer and is associated with apoptosis (programmed cell death), inflammation and the ability of cells to proliferate and stick to each other (hallmarks of cancer growth).

IL4 -- This Interleukin 4 gene is associated with tumor growth, blood vessel development and cancer cell migration.

CRY1 -- Cytochrome 1 is a gene that impacts the circadian rhythm and thereby may affect androgen levels, which are known to be involved in prostate cancer progression.

ARVCF -- This gene is a member of the catenin family of proteins, which help the inside and outside of cells "talk" to each other. Increased expression of ARVCF has been shown to disrupt cell adhesion, which may facilitate cancer progression.

Patients who carried four or all five of these genetic markers had a 50 percent higher risk of dying from their prostate cancer than patients who had two or fewer. The risk of dying from prostate cancer increased with the number of SNP genetic variants a patient carried.

"While previous studies have suggested that genetic background influences prostate cancer outcomes, this is the first study to validate genetic markers associated with lethal disease," Stanford said.

"The ability to distinguish patients at elevated risk for having aggressive, life-threatening prostate cancer at the time of diagnosis could improve care for the subset of cases most likely to benefit from aggressive therapy and help avoid overtreatment of patients whose tumors are likely to remain indolent," the authors wrote.

The potential usefulness of the panel of five SNPs in the clinic to stratify patients at higher risk for disease progression now needs to be evaluated in other patient populations. Stanford and colleagues are also planning additional studies of this set of genetic markers to predict adverse prostate cancer outcomes.

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New drug aids gout patients not helped by standard treatments

Islamabad, Sep 2 (Newswire): Injections of pegloticase, a modified porcine enzyme, can produce significant and sustained clinical improvements in 2 out of 5 patients with chronic gout that is resistant to conventional therapies, researchers report in JAMA.

In two controlled clinical trials, pegloticase rapidly lowered high levels of uric acid, the biochemical abnormality in gout, and kept it in the normal range for six months or more in 42 percent of patients receiving the drug every two weeks. Forty percent of patients had complete resolution of at least one of the painful swollen joint nodules, known as tophi, a hallmark of severe gout.

Injections of pegloticase, a modified porcine enzyme, can produce significant and sustained clinical improvements in 2 out of 5 patients with chronic gout that is resistant to conventional therapies, researchers report in the August 17, 2011, issue of JAMA.

In two controlled clinical trials, pegloticase rapidly lowered high levels of uric acid, the biochemical abnormality in gout, and kept it in the normal range for six months or more in 42 percent of patients receiving the drug every two weeks. Forty percent of patients had complete resolution of at least one of the painful swollen joint nodules, known as tophi, a hallmark of severe gout.

"This represents the first effective therapy for a group of patients who previously had no options at all," said the study's senior author, Michael A. Becker, MD, professor of medicine at the University of Chicago. "This is for patients with severe gout, including major disabilities and high levels of pain. Many of these people had dramatic responses within months, some with complete resolution of tophi, as well as reduced levels of pain and disability. The rapidity of these outcomes is unheard of."

"People are dramatically helped by the drug," said rheumatologist John S. Sundy, MD, PhD, director of the Duke Clinical Research Unit and lead author of the study. The drug's response among patients who have failed common therapies is typically an "all-or-nothing result," he added, "providing marked relief for those who benefit."

Becker cautioned that "it's not curative, but it resets the clock, moving the hands back on a patient's struggle with a progressive disease."

Once associated with European royal families, gout is increasingly a middle-class American disease, with connections to obesity, hypertension, diabetes, heart disease and alcohol abuse. An estimated 6 million people, about 2 percent of the U.S. adult population, have gout, a number that has increased by about 50 percent since 1990.

The disease is caused by a gradual accumulation of uric acid. When levels exceed the saturation point, uric acid forms tiny urate crystals, like thousands of little needles, that deposit in the lining of joints and other tissues. The crystals can cause inflammation, swelling and intense pain. A favorite target is at the base of the big toe, a common site for acute arthritic attacks and tophi.

There are medications for chronic gout that block the synthesis of uric acid or help the kidneys remove it. For about 3 percent of people with gout, however, these drugs either are ineffective or cause intolerable side effects. This leaves about 120,000 to 180,000 patients in the United States with chronic disabling disease and, until recently, no effective therapy.

Pegloticase -- approved by the FDA in September 2010 for the treatment of severe, refractory gout -- was designed to meet that need, filling a gap left by nature. Most species, except for humans and a few other primates, produce the enzyme urate oxidase (also know as uricase). This enzyme converts uric acid to allantoin, which is far more soluble in fluids and can be easily excreted. "It essentially digests uric acid," Becker said.

Scientists at Duke, led by Michael Hershfield, MD, developed the compound and spent decades to fine tune the drug and usher it to market. They modified the version of the enzyme from pigs and wrapped it in polyethylene glycol to protect it from being degraded or attacked by the patient's immune system. The coating extends the half-life of the enzyme from eight hours to 10 to 12 days, so patients need an injection just once every two weeks, making this drug suitable for long-term treatment.

When pegloticase is injected into patients with severe gout, their uric acid levels return to normal within 24 hours. This can lead to gradual dissolution of uric-acid crystals and eventual resolution of gout symptoms.

The two parallel clinical trials focused on 212 patients from 56 rheumatology practices in the United States, Canada and Mexico. They enrolled patients with severe gout and high uric-acid levels who were not helped by or couldn't tolerate standard treatments. Patients were divided into three groups. One group was injected with 8 milligrams of pegloticase every two weeks, one group received pegloticase every month and one group got a placebo -- injections of saline but no actual drug. All participants were enrolled for six months of treatment.

Although uric-acid levels fell to normal ranges within 24 hours in all patients who received the drug, for some patients the drug soon lost its beneficial effect. In 42 percent of patients who got the drug every two weeks, however, uric-acid levels stayed within normal ranges for at least 80 percent of the six-month period. In 35 percent of those who got injections once a month, uric-acid levels remained low for 80 percent of the trial period. Patients who received a placebo had no change in levels.

Forty percent of biweekly injection patients and 21 percent of those getting monthly injections had complete resolution of one or more tophi within six months, compared with 7 percent of patients receiving placebo. Patients who received the drug also reported improved physical function and quality of life.

Nine out of 10 patients, however, had at least one adverse event. The most common were gout flares -- brief, treatable attacks of pain and inflammation. These declined after the first three months of treatment.

The second most common side effect, and the primary reason for patients to withdraw from the study, was an infusion-related reaction; 26 percent of treated patients, most of whom had already stopped responding to the drug, developed an immune response to injection of the foreign protein. Although patients were given medications to reduce the risk and severity of an immune response, about 5 percent of biweekly and 8 percent of monthly patients had a serious reaction. These all resolved completely.

Nearly all of the patients in the study had multiple cardiovascular risk factors and seven patients died during the trial period. The authors recommend "measures to stabilize cardiovascular problems prior to and during treatment."

Most patients eventually developed antibodies against the drug, which suggests that it may be difficult to repeat treatment months or years later. Additional research is aimed at learning the optimum duration of treatment and bolstering the drug's response in more patients.

Despite the risks, "this is an advance -- a significant advance," Becker said.

Sundy added: "This is a group of people for whom there has not been another option for a long time."

The cost of pegloticase, sold as Krystexxa by Savient Pharmaceuticals, is about $60,000 for a year of treatment. Most patients complete treatment within six to eight months.

It may also be very useful for transplant patients, Becker said. About 10 percent of transplant recipients get gout and many can't take the standard medications because they interfere with the drugs that prevent rejection.

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