Day: 12/10/2012

11 Secret Documents Americans Deserve to See.

Posted by

0


Many documents produced by the U.S. government are confidential and not released to the public for legitimate reasons of national security.  Others, however, are kept secret for more questionable reasons.  The fact that presidents and other government officials have the power to deem materials classified provides them with an opportunity to use national security as an excuse to suppress documents and reports that would reveal embarrassing or illegal activities.

 

I’ve been collecting the stories of unreleased documents for several years. Now I have chosen 11 examples that were created—and buried—by both Democratic and Republican administrations and which cover assassinations, spying, torture, 50-year-old historical events, presidential directives with classified titles and…trade negotiations.

 

1. Obama Memo Allowing the Assassination of U.S. Citizens      

When the administration of George W. Bush was confronted with cases of Americans fighting against their own country, it responded in a variety of ways. John Walker Lindh, captured while fighting with the Taliban in December 2001, was indicted by a federal grand jury and sentenced to 20 years in prison. José Padilla was arrested in Chicago in May 2002 and held as an “enemy combatant” until 2006 when he was transferred to civilian authority and, in August 2007, sentenced to 17 years in prison for conspiring to support terrorism. Adam Gadahn, who has made propaganda videos for al-Qaeda, was indicted for treason in 2006 and remains at large.

 

After he took over the presidency, Barack Obama did away with such traditional legal niceties and decided to just kill some Americans who would previously have been accused of treason or terrorism. His victims have included three American citizens killed in Yemen in 2011 by missiles fired from drones: U.S.-born anti-American cleric Anwar al-Awlaki, Samir Khan, an al-Qaeda propagandist from North Carolina, and Awlaki’s 16-year-old son, Abdulrahman al-Awlaki.

 

Obama justified his breach of U.S. and international law with a 50-page memorandum prepared by the Justice Department’s Office of Legal Counsel.  Attorney General Eric Holder argued that the killing of Awlaki was legal because he was a wartime enemy and he could not be captured, but the legal justification for this argument is impossible to confirm because the Obama administration has refused to release the memo.

 

2. The Obama Interpretation of Section 215 of the Patriot Act

Section 215 of the Patriot Act allows the FBI, in pursuit of spies and terrorists, to order any person or entity to turn over “any tangible things” without having to justify its demands by demonstrating probable cause. For example, a library can be forced to reveal who borrowed a book or visited a web site. According to Section 215, the library is prohibited from telling anyone what it has turned over to the FBI.

 

The Obama administration has created a secret interpretation of Section 215 that goes beyond the direct wording of the law to include other information that can be collected. Democratic Senator Ron Wyden of Oregon, who, as a member of the Senate Intelligence Committee, was briefed about this secret interpretation, urged the president to make it public. “I want to deliver a warning this afternoon,” he said. “When the American people find out how their government has secretly interpreted the Patriot Act, they will be stunned and they will be angry.”

 

Wyden and Sen. Mark Udall of Colorado, also a Democrat, have implied that the Obama administration has expanded the use of Section 215 to activities other than espionage and terrorism. In a letter to Attorney General Eric Holder, Wyden and Udall wrote that “there is now a significant gap between what most Americans think the law allows and what the government secretly claims the law allows. This is a problem, because it is impossible to have an informed public debate about what the law should say when the public doesn’t know what its government thinks the law says.”
3. 30-page Summary of 9/11 Commission Interview with Bush and Cheney

You would have thought that, in the interests of the nation, the Bush administration would have demanded a thorough investigation of the terrorist attacks of September 11, 2001, the deadliest assault ever on U.S. soil. Instead, they fought tooth and nail against an independent investigation. Public pressure finally forced President George W. Bush to appoint a bipartisan commission that came to be known as the 9/11 Commission.  It was eventually given a budget of $15 million…compared to the $39 million spent on the Monica Lewinsky/Bill Clinton investigation. When the commission completed its work in August 2004, the commissioners turned over all their records to the National Archives with the stipulation that the material was to be released to the public starting on January 2, 2009. However, most of the material remains classified. Among the more tantalizing still-secret documents are daily briefings given to President Bush that reportedly described increasingly worried warnings of a possible attack by operatives of Osama bin Laden.

 

Another secret document that the American people deserve to see is the 30-page summary of the interview of President Bush and Vice-President Dick Cheney conducted by all ten commissioners on April 29, 2004.  Bush and Cheney refused to be interviewed unless they were together. They would not testify under oath and they refused to allow the interview to be recorded or transcribed.  Instead the commission was allowed to bring with them a note taker. It is the summary based on this person’s notes that remains sealed.

 

4. Memos from President George W. Bush to the CIA Authorizing Waterboarding and other Torture Techniques

Four days after the terrorist attacks of September 11, 2001, President George W. Bush signed a “memorandum of notification” (still secret) that authorized the CIA to do what it needed to fight al-Qaeda.  However the memo did not address what interrogation and torture techniques could be used on captured suspects. By June 2003, Director George Tenet and others at the CIA were becoming worried that if their seemingly illegal tactics became known to the public, the White House would deny responsibility and hang the CIA out to dry.  After much discussion, Bush’s executive office handed over two memos, one in 2003 and another in 2004, confirming White House approval of the CIA interrogation methods, thus giving the CIA “top cover.” It is not known if President Bush himself signed the memos.

 

5. 1,171 CIA Documents Related to the Assassination of President Kennedy

It’s been 49 years since President John F. Kennedy was shot to death in Dallas, yet the National Archives and Records Administration (NARA) insists that more than one thousand documents relating to the case should not be released to the public until NARA is legally required to do so in 2017…unless the president at that time decides to extend the ban.  It would appear that some of the blocked material deals with the late CIA agent David Phillips, who is thought to have dealt with Lee Harvey Oswald in Mexico City six weeks before the assassination.

 

6. Volume 5 of the CIA’s History of the Bay of Pigs Fiasco

In the late 1970s and early 1980s, CIA historian Dr. Jack B. Pfeiffer compiled a multi-volume history of the failed US attempt to invade Cuba in April 1961.  In August 2005, the National Security Archive at George Washington University, citing the Freedom of Information Act, requested access to this history.  The CIA finally released the information almost six years later, in July 2011. However it refused to release Volume V, which is titled “CIA’s Internal Investigation of the Bay of Pigs Operations.”  Although more than 50 years have passed since the invasion, the U.S. District Court for the District of Columbia ruled that Volume V is exempt from the Freedom of Information Act because it “is covered by the deliberative process privilege” which “covers documents reflecting advisory opinions, recommendations and deliberations comprising part of a process by which governmental decisions and policies are formulated.”

 

7. National Security Decision Directives with Classified Titles

The day before he left the White House on January 20, 1993, President George H. W. Bush issued National Security Directive (NSD) #79, a document so secret that even its title remains classified almost 20 years later. The same goes for National Security Directive #77, issued a few days earlier, as well as four others issued in 1989 (#11, 13a, 19a and 25a). If the “a”s are any indication of the subjects, it is worth noting that NSD 13 dealt with countering cocaine trafficking in Peru; NSD 19 dealt with Libya and NSD 25 with an election in Nicaragua.

 

President Ronald Reagan also issued six NSDs with classified titles, and President Bill Clinton issued 29.  President George W. Bush issued two such NSDs, presumably shortly after the terrorist attacks of September 11, 2001. President Barack Obama has issued at least seven Presidential Policy Directives with classified titles.

 

8. Major General Douglas Stone’s 700-Page Report on Prisoners Held in Afghanistan

Marine Corps General Douglas Stone earned positive reviews for his revamping of detention operations in Iraq, where he determined that most of the prisoners held by the United States were not actually militants and could be taught trades and rehabilitated. Based on his success in Iraq, Stone was given the task of making an evaluation of detainee facilities in Afghanistan. His findings, conclusions and recommendations were included in a 700-page report that he submitted to the U.S. Central Command in August 2009. According to some accounts of the report, Stone determined that two-thirds of the Afghan prisoners were not a threat and should be released. However, three years after he completed it, Stone’s report remains classified.

 

9. Detainee Assessment Briefs for Abdullah Tabarak and Abdurahman Khadr

In 2011, WikiLeaks released U.S. military files known as Detainee Assessment Briefs (DABs), which describe the cases of 765 prisoners held at Guantánamo Bay. However, there were actually 779 prisoners. So what happened to the files for the other fourteen? Andy Worthington, author of The Guantanamo Files, has noted that two of the fourteen missing stories are especially suspicious: those of Abdullah Tabarak and Abdurahman Khadr.

 

Tabarak, a Moroccan, was allegedly one of Osama bin Laden’s long-time bodyguards, and took over bin Laden’s satellite phone in order to draw U.S. fire to himself instead of to bin Laden when U.S. forces were chasing the al-Qaeda leader in the Tora Bora mountains in December 2001.  Captured and sent to Guantánamo, Tabarak was mysteriously released, sent back to Morocco in July 2003, and set free shortly thereafter.

 

Abdurahman Khadr, the self-described “black sheep” of a militant family from Canada, was 20 years old when he was captured in Afghanistan and turned over to American forces. He has said that he was recruited by the CIA to become an informant at Guantánamo and then in Bosnia. When the CIA tried to send him to Iraq, he refused and returned to Canada. His younger brother, Omar, was 15 years old when he was captured in Afghanistan and accused of killing an American soldier, Sergeant First Class Christopher Speer, during a firefight.  He was incarcerated at Guantánamo for almost ten years until he was finally released to Canadian custody on September 29, 2012.

 

10. FBI Guidelines for Using GPS Devices to Track Suspects

On January 23, 2012, in the case of United States v. Jones, the Supreme Court ruled unanimously that attaching a GPS device to a car to track its movements constitutes a “search” and is thus covered by the Fourth Amendment protecting Americans against “unreasonable searches and seizures.”  But it did not address the question of whether the FBI and other law enforcement agencies must obtain a warrant to attach a GPS device or whether it is enough for an agent to believe that such a search would turn up evidence of wrongdoing.

 

A month later, at a symposium at the University of San Francisco, FBI lawyer Andrew Weissman announced that the FBI was issuing two memoranda to its agents to clarify how the agency would interpret the Supreme Court decision. One memo dealt with the use of GPS devices, including whether they could be attached to boats and airplanes and used at international borders. The second addressed how the ruling applied to non-GPS techniques used by the FBI.

 

The ACLU, citing the Freedom of Information Act, has requested publication of the two memos because they “will shape not only the conduct of its own agents but also the policies, practices and procedures of other law enforcement agencies—and, consequently, the privacy rights of Americans.”

 

11. U.S. Paper on Negotiating Position on the Free Trade Agreement of the Americas

The subject of international trade negotiations is one that makes most people’s eyes glaze over. So why is the Obama administration fighting so hard to keep secret a one-page document that relates to early negotiations regarding the Free Trade Agreement of the Americas (FTAA), an accord that was proposed 18 years ago and about which public negotiations ended in 2005? All we know is that the document “sets forth the United States’ initial proposed position on the meaning of the phrase ‘in like circumstances.’” This phrase “helps clarify when a country must treat foreign investors as favorably as local or other foreign investors.”

 

Responding to a Freedom of Information Act lawsuit filed by The Center for International Environmental Law, DC District Judge Richard W. Roberts ordered the Office of the United States Trade Representative (USTR) to release the document, but the Obama administration has refused, claiming that disclosure “reasonably could be expected to result in damage to the national security” because all the nations involved in the failed negotiations agreed to keep all documents secret until December 31, 2013…“unless a country were to object to the release of one of its own documents at that time.” Judge Roberts ruled that the USTR has failed to present any evidence that release of the document would damage national security.

 

Most likely, the Obama administration is afraid that release of the document would set a precedent that could impede another secret trade negotiation, the Trans-Pacific Partnership (TPP), also known as the Trans-Pacific Strategic Economic Partnership Agreement, which seeks to establish a free trade zone among the U.S., New Zealand, Chile, Singapore, Brunei, Australia, Peru, Vietnam, Malaysia and possibly Canada, Mexico and Japan.

PROVENGE activates the immune system to fight advanced prostate cancer.

Posted by

0


 

•

 PROVENGE is the first and only FDA-approved personalized immunotherapy for asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer

•

 PROVENGE is made by culturing a patient’s own immune cells with a recombinant antigen* that is prostate specific. When infused into the patient, PROVENGE activates T cells to target and attack prostate cancer cells.
INDICATION

 Provenge_C_honc_rebuild_img_1

PROVENGE® (sipuleucel-T) is approved by the FDA as an autologous cellular immunotherapy for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant (hormone refractory) prostate cancer.
IMPORTANT SAFETY INFORMATION

PROVENGE is intended solely for autologous use and is not routinely tested for transmissible infectious diseases.

In controlled clinical trials, serious adverse events reported in the PROVENGE group included acute infusion reactions (occurring within 1 day of infusion) and cerebrovascular events. Severe (Grade 3) acute infusion reactions were reported in 3.5% of patients in the PROVENGE group. Reactions included chills, fever, fatigue, asthenia, dyspnea, hypoxia, bronchospasm, dizziness, headache, hypertension, muscle ache, nausea, and vomiting. No Grade 4 or 5 acute infusion reactions were reported in patients in the PROVENGE group.

The most common adverse events (incidence ≥ 15%) reported in the PROVENGE group were chills, fatigue, fever, back pain, nausea, joint ache, and headache.
REFERENCES
 

1.

 Kantoff PW, Higano CS, Shore ND, et al; for the IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010;363:411-422.

 

 

2.

 NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. V.3.2012. National Comprehensive Cancer Network Web site. www.nccn.org. Accessed April 26, 2012.

 

Two-year data show new Novartis drug Jakavi® significantly reduced myelofibrosis disease burden and suggest overall survival advantage.

Posted by

0


  • Jakavi demonstrated rapid reductions in spleen size and improved quality of life in Phase III studies, with results sustained over two years

 

  • COMFORT-II follow-up results show Jakavi may improve overall survival vs. best available therapy

 

  • MF is a life-threatening blood cancer associated with progressive, debilitating symptoms that severely impact quality of life and reduce overall survival

 

  • Until recently, treatment options have been very limited – Jakavi is now approved in the EU and Canada with additional worldwide regulatory filings underway 

 

Novartis today announced long-term follow-up data from the COMFORT-I and COMFORT-II Phase III studies in myelofibrosis. In these studies, Jakavi® (INC424, ruxolitinib) treatment resulted in sustained reductions in spleen size, a hallmark of myelofibrosis, while also improving quality of life and extending overall survival compared to placebo or the best available therapy (BAT).

 

Results are being presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition in Atlanta.

 

A two-year follow-up analysis of COMFORT-II showed Jakavi was associated with sustained reductions in splenomegaly (enlarged spleen). Overall, 48.3% of patients treated with Jakavi achieved a >=35% reduction in spleen volume, and the majority of reductions were sustained with continued treatment over two years. In a rigorous intent-to-treat analysis, Jakavi-treated patients showed an overall survival advantage compared to patients receiving BAT (HR=0.51; 95% CI, 0.26-0.99; p=0.041)[1], which was defined by protocol as any commercially available agent (monotherapy or in combination) or no therapy at all. A total of 61.6% of BAT patients switched to Jakavi treatment, but remained categorized as BAT patients during the follow-up analyses[1].

 

“As these Phase III studies continue over the long term, it is encouraging to see how treatment with Jakavi consistently alleviates the myelofibrosis disease burden and may improve overall survival,” said Dr. Francisco Cervantes, Hematology Department, Hospital Clínic, IDIBAPS, University of Barcelona. “Just one year ago, we didn’t have a truly effective treatment to offer our patients with myelofibrosis. Now, it appears we can significantly improve a patient’s quality of life while also potentially extending their life.”

 

In COMFORT-I, which compared the use of Jakavi versus placebo, researchers presented long-term follow-up data evaluating the efficacy and safety of Jakavi. Similar to COMFORT-II, Jakavi was associated with sustained reductions in spleen volume. Mean spleen volume reduction in the Jakavi arm was 31.6% at week 24, and maintained through week 96 (34.9%)[2]. Among patients with a >=35% reduction in spleen volume, response was maintained with a median duration of 108 weeks. The study demonstrated a continued overall survival benefit in favor of Jakavi, as 83% of patients on Jakavi survived at the 102 week follow-up period, compared to 73% of patients on placebo (HR=0.58; 95% CI, 0.36-0.95; p=0.028)[2]. Overall survival favored Jakavi across subgroups, including starting dose as well as baseline risk status and hemoglobin[2].

 

“The COMFORT program, which supported the European Commission approval for Jakavi, is the most extensive clinical trial program in myelofibrosis to date and continues to demonstrate significant results for Jakavi-treated patients,” said Hervé Hoppenot, President, Novartis Oncology. “We are encouraged by these findings and look forward to evaluating how Jakavi may help patients with other myeloproliferative neoplasms associated with a similar mechanism of disease.”

 

Myelofibrosis develops when uncontrolled signaling in the JAK pathway – which regulates blood cell production – causes bone marrow scarring and faulty blood cell production, resulting in severe complications. Jakavi directly targets an underlying mechanism of myelofibrosis, significantly reducing splenomegaly and improving debilitating symptoms regardless of JAK mutational status, disease subtype or any prior treatment, including hydroxyurea[3],[4],[5],[6].

 

While Jakavi has proven to provide patient benefits regardless of mutational status, an analysis of patients with the JAK2V617F mutation within the COMFORT-II study was also presented at ASH. Findings demonstrate the disease-modifying effects of Jakavi.  Patients bearing the JAK2V617F mutation who received Jakavi had greater reductions in the presence of cancerous cells with the mutated JAK2V617F allele (allele burden) compared with BAT[5]. Allele burden reductions among Jakavi-treated patients were gradual and sustained over the duration of the study, whereas BAT-treated patients demonstrated zero reductions. Among patients with >=20% allele burden reduction, sustained spleen volume reductions were observed to week 72[5].

 

COMFORT-II Long-Term Study Background

The COMFORT-II (COntrolled MyeloFibrosis Study with ORal JAK Inhibitor Therapy) study randomized 219 patients to receive Jakavi (15 or 20 mg BID) or BAT (2:1 randomization for Jakavi vs. BAT). A total of 73.3% (107/146) of patients in the Jakavi arm entered the extension phase vs. 61.6% (45/73) in the BAT arm, and 55.5% (81/146) of those originally randomized to Jakavi remained on treatment at the time of this analysis[1]. Overall survival was estimated using the Kaplan-Meier method. In the analysis of COMFORT-II data examining JAK2V617 allele burden reduction, allele burden was measured from blood samples using allele-specific quantitative real-time polymerase chain reaction (qPCR)[5].

 

No specific long-term safety signals emerged during the two-year follow-up period. In the primary analysis of the COMFORT-II study published in The New England Journal of Medicine in February 2012 (median treatment duration of 50.1 weeks; Jakavi, 51.4 weeks; BAT, 45.1 weeks), the most common grade 3/4 hematologic adverse events (AEs) in either arm (Jakavi, BAT) were anemia (42.4%; 31.4%) and thrombocytopenia (8.3%; 7.2%), and were manageable with either dose reduction or occasional interruption[4]. In the Jakavi arm, mean hemoglobin levels decreased over the first 12 weeks of treatment and then recovered to levels similar to the BAT from week 24 onward[4].

 

One patient in each arm discontinued for thrombocytopenia, and no patients discontinued for anemia. One week after discontinuing Jakavi, these patients experienced a return of myelofibrosis symptoms that were present before initiating therapy. Since the core study has completed, all patients either entered the extension phase or discontinued from the study. A total of 107 of the 146 patients on Jakavi entered the extension phase in addition to 45 of the 73 patients previously treated with BAT (median treatment duration of 83.3 weeks; Jakavi, 111.4 weeks [randomized and extension phases]; BAT, 45.1 weeks [randomized treatment only per primary analysis]. Grade 3/4 hematologic abnormalities in the extension phase for Jakavi were consistent with the primary analysis: anemia (40.4%); lymphopenia (22.6%) and thrombocytopenia (9.6%)[1].

 

COMFORT-I Long-Term Study Background

This study randomized 309 patients to Jakavi or placebo. The primary analysis occurred when all patients completed 24 weeks of therapy, and all patients receiving placebo were eligible to cross over to Jakavi after the primary analysis. Quality of life was evaluated beyond week 24 using the European Organization for Research and Treatment of Cancer QoL Questionnaire-Core 30, and overall survival was assessed according to original randomized treatment[2].

 

The AE profile with long-term treatment is consistent with what has been previously reported[2]. Of 34 patients randomized to Jakavi who discontinued after the primary analysis, 4 discontinued for an AE. In patients who continued on Jakavi therapy, anemia and thrombocytopenia remained the most frequently reported AEs. New onset of grade 3 or 4 anemia and thrombocytopenia was reported in 12 and 5 patients, respectively. One patient discontinued for anemia. Overall, among all patients randomized to Jakavi, grade 3 and 4 anemia – regardless of baseline hemoglobin – was reported in 37.4% and 14.8% of patients, respectively. Similarly, grade 3 and 4 thrombocytopenia was reported in 11.0% and 5.2% of patients, respectively. These rates were similar to those reported in the primary analysis. By week 36, the proportion of patients receiving red blood cell transfusions decreased to the level seen with placebo and remained stable thereafter[2].

 

Rates of non-hematologic AEs adjusted for increased follow-up duration remained similar to those seen at the time of the primary data analysis[2]. No additional cases of acute myeloid leukemia (AML) in patients randomized to Jakavi were reported. Two patients originally randomized to placebo developed AML, 21 and 178 days after crossover to Jakavi. There continued to be no reports of a withdrawal syndrome after Jakavi discontinuation[2].

 

About Myelofibrosis

Myelofibrosis is a life-threatening blood cancer with a poor prognosis and limited treatment options[7],[8]. Studies show that patients with myelofibrosis have a decreased life expectancy, with a median overall survival of 5.7 years[9]. Although allogeneic stem cell transplantation may cure myelofibrosis, the procedure is associated with significant morbidity and transplant-related mortalityand is available to less than 5% of patients who are young and fit enough to undergo the procedure[10].

 

About Jakavi  

Jakavi® (INC424, ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine kinases[4] and was approved by the European Commission in August 2012 for the treatment of disease-related splenomegaly or symptoms in adult patients with primary myelofibrosis (also known as chronic idiopathic myelofibrosis), post-polycythemia vera myelofibrosis or post-essential thrombocythemia myelofibrosis. Jakavi is available in more than 30 countries including the European Union and Canada, with additional global regulatory filings underway.

 

Novartis licensed INC424 (ruxolitinib) from Incyte Corporation for development and commercialization outside the United States. Both the European Commission and the US Food and Drug Administration (FDA) granted INC424 (ruxolitinib) orphan drug status for myelofibrosis. Jakavi is marketed in the United States by Incyte Corporation under the name Jakafi® for the treatment of patients with intermediate or high-risk myelofibrosis.

 

The recommended starting dose for Jakavi is 15 mg twice daily for patients with a platelet count between 100,000cubic millimeters (mm3) and 200,000 mm3,and 20 mg twice daily for patients with a platelet count of >200,000 mm3. Doses may be titrated based on safety and efficacy. There is limited information to recommend a starting dose for patients with platelet counts between 50,000/mm3 and <100,000/mm3. The maximum recommended starting dose in these patients is 5 mg twice daily and patients should be titrated cautiously[11].

 

Jakavi is a registered trademark of Novartis AG in countries outside the United States. Jakafi is a registered trademark of Incyte Corporation.

 

Jakavi® Important Safety Information

Jakavi® can cause serious side effects, including a decrease in blood cell count and infections. Complete blood count monitoring is recommended. Dose reduction or interruption may be required in patients with severe hepatic or renal impairment or in patients developing hematologic adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose reductions are also recommended when Jakavi is co-administered with strong CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not recommended and women should avoid becoming pregnant during Jakavi therapy. Women taking Jakavi should not breast feed.

 

The most common adverse drug reactions, occurring at any level of severity (incidence >10%) are urinary tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia, dizziness, headache, alanine aminotransaminase increased, asparte aminotransferase increased, bruising, bleeding and increased blood pressure. Other common adverse drug reactions (incidence 1 to 10%) are herpes zoster, weight gain, flatulence and tuberculosis (1%).

 

Please see full Prescribing Information for Jakavi available at www.jakavi.com.

 

References

[1] Cervantes, F, et al. Long-Term Safety, Efficacy, and Survival Findings From COMFORT-II, a Phase 3 Study Comparing Ruxolitinib with Best Available Therapy (BAT) for the Treatment of Myelofibrosis (MF).  Blood. 2012. Abstract #801. American Society of Hematology (ASH) 2012 Annual Meeting. Atlanta, GA.

[2] Verstovsek S et al. Long-Term Outcome of Ruxolitinib Treatment in Patients with Myelofibrosis: Durable Reductions in Spleen Volume, Improvements in Quality of Life, and Overall Survival Advantage in COMFORT-I. Blood. 2012. Abstract #800. ASH 2012 Annual Meeting. Atlanta, GA.

[3] Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012 March 1: 366:799-807.

[4] Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med. 2012: March 1;366:787-98.

[5] Vannucchi A, Kiladjian JJ, Gisslinger H, et al. Reductions in JAK2V617F Allele Burden with Ruxolitinib Treatment in COMFORT-II, a Phase III Study Comparing the Safety and Efficacy of Ruxolitinib to Best Available Therapy (BAT). 2012. Abstract #802. ASH 2012. Annual Meeting, Atlanta, GA.

[6] Harrison C, Kiladjian JJ, Gisslinger H, et al. Association of Cytokine Levels and Reductions in Spleen Size in COMFORT-II, a Phase 3 Study Comparing Ruxolitinib to Best Available Therapy (BAT). Abstract # 6625. American Society of Clinical Oncology 2012 Annual Meeting, Chicago, IL.

[7] Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 & JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September 16;363(12):1117-1127.

[8] Mesa RA, Schwagera S, Radia D, et al. The Myelofibrosis Symptom Assessment Form (MFSAF): an evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosis. Leuk Res. 2009;33:1199-1203.

[9] Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009;113:2895-2901.

[10] Patriarca F, Bacigalupo A, Sperotto A, et al. Allogeneic hematopoietic stem cell transplantation in myelofibrosis: the 20-year experience of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica. 2008;93(10):1514-1522.

[11] JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis Pharma AG; 2012.

Source: Novartis newsletter.

Climate Models Project Increase in U.S. Wildfire Risk.

Posted by

0


Scientists using NASA satellite data and climate models have projected drier conditions likely will cause increased fire activity across the United States in coming decades. Other findings about U.S. wildfires, including their amount of carbon emissions and how the length and strength of fire seasons are expected to change under future climate conditions, were also presented Tuesday at the annual meeting of the American Geophysical Union in San Francisco.

Doug Morton of NASA’s Goddard Space Flight Center in Greenbelt, Md., presented the new analysis of future U.S. fire activity. The analysis was based on current fire trends and predicted greenhouse gas emissions.

“Climate models project an increase in fire risk across the U.S. by 2050, based on a trend toward drier conditions that favor fire activity and an increase in the frequency of extreme events,” Morton said.

The analysis by Morton and colleagues used climate projections, prepared for the Fifth Assessment Report of the United Nations Intergovernmental Panel on Climate Change, to examine how dryness, and therefore fire activity, is expected to change.

The researchers calculated results for low and high greenhouse gas emissions scenarios. In both cases, results suggest more fire seasons that are longer and stronger across all regions of the U.S. in the next 30-50 years. Specifically, high fire years like 2012 would likely occur two to four times per decade by mid-century, instead of once per decade under current climate conditions.

Through August of this year, the U.S. burned area topped 2.5 million hectares (6.17 million acres), according to a fire emissions database that incorporates burned area estimates produced from observations by the Moderate Resolution Imaging Spectroradiometer instruments on NASA’s Aqua and Terra satellites. That is short of the record 3.2 million hectares (7.90 million acres) burned in 2011, but exceeds the area burned during 12 of the 15 years since record keeping began in 1997. This and other satellite records, along with more refined climate and emissions models, are allowing scientists to tease out new information about fire trends.

“Fire is an inherently global phenomenon, and the only practical way to track large-scale patterns and changes in fire activity is with satellites,” says Louis Giglio of the University of Maryland at College Park and Goddard.

As the U.S. land area burned by fire each year has increased significantly in the past 25 years, so too have the emissions. Carbon dioxide emissions from wildfires in the western U.S. have more than doubled since the 1980s, according to Chris Williams of Clark University in Worcester, Mass.

The satellite-based view allowed Williams and his colleagues to quantify how much carbon has been released from fires in the U.S. West. The team used data on fire extent and severity derived from Landsat satellites to calculate how much biomass is burned and killed, and how quickly the associated carbon was released to the atmosphere. The team found carbon emissions from fires have grown from an average of 8 teragrams (8.8 million tons) per year from 1984 to 1995 to an average of 20 teragrams (22 million tons) per year from 1996 to 2008, increasing 2.4 times in the latter period.

“With the climate change forecast for the region, this trend likely will continue as the western U.S. gets warmer and drier on average,” Williams said. “If this comes to pass, we can anticipate increased fire severity and an even greater area burned annually, causing a further rise in the release of carbon dioxide.”

Researchers expect a drier and more wildfire-prone U.S. in future decades. Previous research confirmed the connection between the measure of an environment’s potential evaporation, or dryness, and fire activity.

From a fire and emissions management perspective, wildfires are not the entire U.S. fire story, according to research by Hsiao-Wen Lin of the University of California at Irvine. Satellite data show agricultural and prescribed fires are a significant factor and account for 70 percent of the total number of active fires in the continental U.S. Agricultural fires have increased 30 percent in the last decade.

In contrast with wildfires, agricultural and prescribed fires are less affected by climate, especially drought, during the fire season.

“That means there is greater potential to manage fire emissions, even in a future, drier climate with more wildfires. We need to use cost-benefit analysis to assess whether reductions in agricultural fire emissions — which would benefit public health — would significantly impact crop yields or other ecosystem services,” Lin said.

Source:NASA

Yes, You Can Hack a Pacemaker (and Other Medical Devices Too).

Posted by

0


On Sunday’s episode of the Emmy award-winning show Homeland, the Vice President of the United States is assassinated by a group of terrorists that have hacked into the pacemaker controlling his heart. In an elaborate plot, they obtain the device’s unique identification number. They then are able to remotely take control and administer large electrical shocks, bringing on a fatal heart attack.

Viewers were shocked — many questioned if something like this was possible in real life. In short: Yes (except, the part about the attacker being halfway across the world is questionable). For years, researchers have been exposing enormous vulnerabilities in Internet-connected implanted medical devices.

There are millions of people who rely on these brilliant technologies to stay alive. But as we put more electronic devices into our bodies, there are serious security challenges that must be addressed. We are familiar with the threat that cyber-crime poses to the computers around us — however, we have not yet prepared for the threat it may pose to the computers inside of us.

Implanted devices have been around for decades, but only in the last decade have these devices become virtually accessible. While they allow for doctors to collect valuable data, many of these devices were distributed without any type of encryption or defensive mechanisms in place. Unlike a regular electronic device that can be loaded with new firmware, medical devices are embedded inside the body and require surgery for “full” updates. One of the greatest constraints to adding additional security features is the very limited amount of battery power available.

Thankfully, there have been no recorded cases of a death or injury resulting from a cyber attack on the body. All demonstrations so far have been conducted for research purposes only. But if somebody decides to use these methods for nefarious purposes, it may go undetected.

Marc Goodman, a global security expert and the track chair for Policy, Law and Ethics at Singularity University, explains just how difficult it is to detect these types of attacks. “Even if a case were to go to the coroner’s office for review,” he asks, “how many public medical examiners would be capable of conducting a complex computer forensics investigation?” Even more troubling was, “The evidence of medical device tampering might not even be located on the body, where the coroner is accustomed to finding it, but rather might be thousands of kilometers away, across an ocean on a foreign computer server.”

Since knowledge of these vulnerabilities became public in 2008, there have been rapid advancements in the types of hacking successfully attempted.

The equipment needed to hack a transmitter used to cost tens of thousands of dollars; last year a researcher hacked his insulin pump using an Arduino module that cost less than $20. Barnaby Jack, a security researcher at McAfee, in April demonstrated a system that could scan for and compromise insulin pumps that communicate wirelessly. With a push of a button on his laptop, he could have any pump within 300 feet dump its entire contents, without even needing to know the devices’ identification numbers. At a different conference, Jack showed how he reverse engineered a pacemaker and could deliver an 830-volt shock to a person’s device from 50 feet away — which he likened to an “anonymous assassination.”

There have also been some fascinating advancements in the emerging field of security for medical devices. Researchers have created a “noise” shield that can block out certain attacks — but have strangely run into problems with telecommunication companies looking to protect their frequencies. There have been the discussions of using ultrasound waves to determine the distance between a transmitted and medical device to prevent far-away attacks. Another team has developed biometric heartbeat sensors to allow devices within a body to communicate with each other, keeping out intruding devices and signals.

But these developments pale in comparison to the enormous difficulty of protecting against “medical cybercrime,” and the rest of the industry is falling badly behind.

In hospitals around the country there has been a dangerous rise of malware infections in computerized equipment. Many of these systems are running very old versions of Windows that are susceptible to viruses from years ago, and some manufacturers will not allow their equipment to be modified, even with security updates, partially due to regulatory restrictions. A solution to this problem requires a rethinking of the legal protections, the loosening of equipment guidelines, as well as increased disclosure to patients.

Government regulators have studied this issue and recommended that the FDA take these concerns into account when approving devices. This may be a helpful first step, but the government will not be able to keep up with the fast developments of cyber-crime. As the digital and physical world continue to come together, we are going to need an aggressive system of testing and updating these systems. The devices of yesterday were not created to protect against the threats of tomorrow.

Source:Forbes

The Politics of Life on Mars.

Posted by

0


Speculation about life on Mars has been rampant this fall. Rumors that the Mars Curiosity Rover may have found evidence of life on Mars have surfaced twice in the past few weeks. The most recent rumor started when a member of the Curiosity team was quoted as saying that they had collected data that was “Earthshaking” and “one for the history books.” This led to a barrage of rumors that Curiosity may have found organic material on Mars and some people even speculated that life had been found. The reality gave no confirmation of life, but the NASA press conference on December 3, 2012 did reveal that some simple organics were found. They were not sure if they were indigenous to Mars, if they may have been residual organics from Earth, or if they had been deposited from other space objects (meteorites) impacting Mars.

Curiosity’s mission should give us the answer to this eventually as it is scheduled to continue for at least another 18 months and was recently “officially” extended indefinitely. This gives Curiosity ample time to sample soil and rocks in some highly promising locations within Gale Crater on Mars. If organics exist there, Curiosity should know within the next few months.

Although Curiosity is not designed to verify life, we are left to wonder — if Curiosity did discover life on Mars, what would be the impact of that discovery to the general public and to the future of human and robotic exploration of Mars?

One thing is certain, it would have a substantial impact, but the nature of that impact could move in many different directions. A popular belief is that if we found life on Mars this would accelerate our goals of sending humans to Mars as well as our robotic efforts, and also might transform our religious and societal beliefs. This isn’t necessarily the case.

Our Place in the Universe

In fact, we have already had a test run for this hypothesis. Back in 1996, scientists announced findings that indicated that they had found fossil evidence of microbial life forms on a Martian meteorite (ALH 84001) that had been found in Antarctica a decade earlier. The story became a media sensation and President Clinton conducted a press conference to discuss the discovery. The announcement certainly did impact our robotic missions planning, but it did little to advance human space flight (we didn’t change directions in human space flight until after the Space Shuttle Columbia disintegrated in the skies over Texas.) The public enthusiasm to the announcement was also very short lived and there is little evidence that it transformed anyone’s religious or societal viewpoint. Would the confirmation of current microbial life be different? Probably not. The public would be engaged for a while (and probably enthusiastically), but the enthusiasm would be relatively short lived. It would likely take the discovery of a higher life form to ignite the type of passionate debate and emotion that was seen in the movie Contact.

Save the Microbes!

Perhaps the greatest impact would be within the mission planning community and among policy makers. Life on Mars will almost certainly make human missions to Mars far more complicated to plan. Planetary protection protocols would be very strict as we planned human missions to Mars. We would have to assure that there would be no forward, nor backward, contamination. This would become a VERY serious issue.

We should expect potential lawsuits from “Mars environmentalists” trying to block ANY human missions to Mars, claiming that we threaten the existence of indigenous Martian life. We would almost certainly hear protestors yelling slogans like “We’ve ruined our own planet, what right do we have to ruin Mars.” This process would probably be similar to the reaction in advance of the launch of the Cassini mission to Saturn back in 1997. This mission was carrying 72 pounds of plutonium dioxide (not the more dangerous plutonium 239 used in nuclear weapons) to power the mission.

The mere fact that there was a form of plutonium on board sparked fears that if the rocket exploded, plutonium would rain down on central Florida. There were numerous protests outside NASA and there even was a legal challenge in the Federal Court of Hawaii challenging the mission’s Environmental Impact Statement. Only after this challenge was rejected in Hawaii and in the Ninth Circuit Court of Appeals was the mission able to launch. Like Cassini, the legal challenges to a Mars mission would be likely to fail. Depending on when the discovery of life was made (is a human mission ten years in the future or one year in the future from the discovery), it could slow down a human mission to Mars. Discovery of life might also serve as a catalyst for various nations to propose contamination protocols in the United Nations – protocols that the US would probably not sign. Again, this would not be enough to stop a human mission to Mars.

That said, the discovery of even microbial life on Mars will be one of the most significant events in human history. And when we do send humans to Mars, we will absolutely need to take precautions and make sure we have solid protocols in place to protect Martian life and protect the crew and Earth from Martian life.

The Human Factor

Still, discovery of life on Mars should not stop a human mission to the Red Planet. On the contrary, it should be a strong case in favor of such a mission. After all, it will be far easier for us to understand the nature of this interplanetary strain of life if we have human scientists there to analyze it. There is also the strong possibility that we will not be able to provide 100 percent verification of Martian life until we send humans to Mars. At least for the foreseeable future, human explorers are the most accurate and efficient method of not only determining the nature of Martian life, but also determining long-term protocols for the protection of both indigenous life forms on other planets and for humanity.

Let’s hope that if such a discovery is made in the next few years, we are able to proceed in as rationale and productive a manner as possible.

Source:http://www.huffingtonpost.com

2012 Awards Presented For Achievements in Earth Remote Sensing.

Posted by

0


NASA and the Department of the Interior’s U.S. Geological Survey (USGS) presented the 2012 William T. Pecora awards for achievement in earth remote sensing to Gilberto Camara of Brazil’s National Institute for Space Research and Leung Tsang of the University of Washington in Seattle.

Camara was recognized for his contributions to remote-sensing leadership as a scientist, program director, manager and agency head. Tsang is one of the world’s leading experts on the theory of microwave remote sensing for geophysical environments. Camara received his award at a meeting of the Group on Earth Observations in Foz do Iguacu, Brazil, on Nov. 22. Tsang received his award Tuesday at the American Geophysical Union meeting in San Francisco.

“Along with the immensely successful Landsat program, the Pecora awards are a testament to the very high value both the U.S. Geological Survey and NASA place in Earth remote sensing,” said USGS Director Marcia McNutt. “As our planet’s water, soil, and ecosystems continue to be stressed by a growing population and changing climate, it is essential we continue into a fifth decade of Earth observation time series and recognize the excellence of remote-sensing experts.”

NASA and the Department of the Interior present individual and group Pecora Awards to honor outstanding contributions in the field of remote sensing and its application to understanding Earth. The award was established in 1974 to honor the memory of William T. Pecora, former USGS director and undersecretary of the Department of the Interior. Pecora was influential in the establishment of the Landsat satellite program, which created a continuous, 40-year record of Earth’s land areas.

“I am sure Dr. Pecora would be pleased if he were here with us today and could see how his vision for innovative remote-sensing technology has been realized in the work of the individuals we are recognizing this year,” said astronaut John Grunsfeld, NASA’s associate administrator for the Science Mission Directorate.

As the former director general of Brazil’s National Institute for Space Research, Camara championed broad, open data-sharing policies and practices within the institute that have significantly influenced other domestic and international organizations to emulate this approach. Camara has advanced the linkages between and among remote-sensing technologies and Geographic Information System technologies and applications.

Camara also supported programs within the institute to link moderate-resolution imagery from the China-Brazil Earth Resources Satellite, Landsat, and other Earth observation missions with the policy needs of the Brazilian government, most notably polices on forestation and deforestation in the Amazon.

Tsang’s contributions to microwave remote sensing have laid the groundwork for improved data analysis and designs of new measurements and satellite observational systems. His work has resulted in numerous societal benefits, including monitoring climate change and improving management of water and agricultural resources. His original and pioneering discoveries have resulted in the publication of more than 260 journal articles and four books.

Tsang also made major advances in rough surface scattering theory and applications to microwave remote sensing of soil and vegetated surfaces. He developed an improved modeling framework for rough surface and vegetation scattering with fast computational methods that can be directly applied to both active and passive microwave remote sensing of soil moisture.

Source:NASA

NASA Mars Rover Fully Analyzes First Martian Soil Samples.

Posted by

0


NASA’s Mars Curiosity rover has used its full array of instruments to analyze Martian soil for the first time, and found a complex chemistry within the Martian soil. Water and sulfur and chlorine-containing substances, among other ingredients, showed up in samples Curiosity’s arm delivered to an analytical laboratory inside the rover.

Detection of the substances during this early phase of the mission demonstrates the laboratory’s capability to analyze diverse soil and rock samples over the next two years. Scientists also have been verifying the capabilities of the rover’s instruments.

The specific soil sample came from a drift of windblown dust and sand called “Rocknest.” The site lies in a relatively flat part of Gale Crater still miles away from the rover’s main destination on the slope of a mountain called Mount Sharp. The rover’s laboratory includes the Sample Analysis at Mars (SAM) suite and the Chemistry and Mineralogy (CheMin) instrument. SAM used three methods to analyze gases given off from the dusty sand when it was heated in a tiny oven. One class of substances SAM checks for is organic compounds — carbon-containing chemicals that can be ingredients for life.

“We have no definitive detection of Martian organics at this point, but we will keep looking in the diverse environments of Gale Crater,” said SAM Principal Investigator Paul Mahaffy of NASA’s Goddard Space Flight Center in Greenbelt, Md.

Curiosity’s APXS instrument and the Mars Hand Lens Imager (MAHLI) camera on the rover’s arm confirmed Rocknest has chemical-element composition and textural appearance similar to sites visited by earlier NASA Mars rovers Pathfinder, Spirit and Opportunity.
Curiosity’s team selected Rocknest as the first scooping site because it has fine sand particles suited for scrubbing interior surfaces of the arm’s sample-handling chambers. Sand was vibrated inside the chambers to remove residue from Earth. MAHLI close-up images of Rocknest show a dust-coated crust one or two sand grains thick, covering dark, finer sand.

“Active drifts on Mars look darker on the surface,” said MAHLI Principal Investigator Ken Edgett of Malin Space Science Systems in San Diego.”This is an older drift that has had time to be inactive, letting the crust form and dust accumulate on it.”

CheMin’s examination of Rocknest samples found the composition is about half common volcanic minerals and half non-crystalline materials such as glass. SAM added information about ingredients present in much lower concentrations and about ratios of isotopes. Isotopes are different forms of the same element and can provide clues about environmental changes. The water seen by SAM does not mean the drift was wet. Water molecules bound to grains of sand or dust are not unusual, but the quantity seen was higher than anticipated.

SAM tentatively identified the oxygen and chlorine compound perchlorate. This is a reactive chemical previously found in arctic Martian soil by NASA’s Phoenix Lander. Reactions with other chemicals heated in SAM formed chlorinated methane compounds — one-carbon organics that were detected by the instrument. The chlorine is of Martian origin, but it is possible the carbon may be of Earth origin, carried by Curiosity and detected by SAM’s high sensitivity design.

“We used almost every part of our science payload examining this drift,” said Curiosity Project Scientist John Grotzinger of the California Institute of Technology in Pasadena. “The synergies of the instruments and richness of the data sets give us great promise for using them at the mission’s main science destination on Mount Sharp.”

NASA’s Mars Science Laboratory Project is using Curiosity to assess whether areas inside Gale Crater ever offered a habitable environment for microbes. NASA’s Jet Propulsion Laboratory in Pasadena manages the project for NASA’s Science Mission Directorate in Washington.

Source:NASA

Extended Treatment of VTE with Apixaban Shows Lower Recurrence vs. Placebo .

Posted by

0


Treatment with apixaban for 1 year reduced recurrence of venous thromboembolism, according to a study in the New England Journal of Medicine sponsored and conducted by the drug maker.

The international study comprised some 2500 patients who had completed 6 to 12 months of anticoagulation therapy and for whom there was equipoise about stopping or continuing. The group were randomized to placebo, or to apixaban at 2.5 mg twice daily, or to apixaban at 5 mg twice daily.

After therapy for 1 year, the rate of the composite primary outcome — symptomatic recurrent VTE or death from any cause — was 11.6% with placebo, versus roughly 4% with each of the apixaban dosages. Rates of major bleeding episodes were similar among the groups (all 0.5% or less).

The authors estimate 14 as the number needed to treat to prevent one episode of recurrent VTE, and 200 as the number needed to treat to cause one episode of major or clinically relevant nonmajor bleeding.

Source: NEJM