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Bernanke Returns to Academic Roots to Justify Fed's Existence
By Rich Miller and Joshua Zumbrun | Bloomberg – 8 hours ago
Federal Reserve Chairman Ben S. Bernanke returns to his roots as a university professor today, seeking to explain and justify the existence of the central bank ahead of the 100th anniversary of its founding next year.
Bernanke will deliver the first of four hour-long lectures on the history of the Fed as part of what public relations specialist Richard Dukas called a "P.R. offensive" to buff the central bank's tarnished image. The Fed is being attacked from both the left and the right, with liberals criticizing it for not doing enough to bring down unemployment, and conservatives blaming it for doing too much and risking faster inflation.
Bernanke's return to the milieu where he spent more than two decades will give the Fed's top policy maker an opportunity to "set the narrative" on the central bank's role during and after the financial meltdown, said Princeton University professor and former Fed Vice Chairman Alan Blinder. "The question of who gets to write the history is an important one."
If Americans lose faith in the Fed's ability to manage the economy and contain inflation, that will rob monetary policy of some of its potency, according to Dana Saporta, director of U.S. economics research for Credit Suisse Securities in New York. Policy has "less effect the less confidence the public has in the Fed," she said.
"Bernanke is getting beaten up and the Fed is getting beaten up," said Dukas, who heads Dukas Public Relations in New York and has 25 years of P.R. experience. "It's smart on his part to try to clearly communicate to the public the role of the Fed during the crisis and what it's been able to do to stabilize the situation."
Education and Outreach
In anticipation of the centennial next year of the 1913 legislation founding the central bank, the Fed has set up an advisory council to discuss ways to mark the occasion with "public education and outreach," said Lisa Oliva, vice president of corporate communications at the Federal Reserve Bank of Richmond. The panel is headed by former Fed chairmen Paul Volcker and Alan Greenspan and includes representatives of academia, business, labor and the public.
Bernanke will be getting a head start on the commemoration with his lectures to about 30 undergraduate students at George Washington University, just blocks away from the Fed's headquarters on Constitution Avenue in Washington.
Today's talk by the former Princeton professor will cover the origins and mission of the Fed. It will be followed on March 22 with a discussion about the central bank after World War II. The final two presentations, on March 27 and 29, will focus on the recent financial crisis and its aftermath.
Live Streamed Lectures
The lecture series -- the brainchild of the Fed and the first by a sitting chairman -- will be streamed live on the central-bank's website and on ustream.tv. Afterwards, it will be posted on the Fed's YouTube page. The central bank said transcripts also will be available.
"I understand he's excited about coming back and being in the classroom," said Tim Fort, the professor in charge of the half-semester class.
Bernanke began preparing in December for the lectures, organizing his thoughts and putting together slides and PowerPoint presentations. Unlike his speeches and Congressional testimonies, he won't be reading from a prepared text.
His return to the classroom comes amid signs that the job market is strengthening. Unemployment has fallen to 8.3 percent, the lowest in three years, while payroll gains during the last six months have been the strongest since 2006.
Good Venue
The venue is a good one for Bernanke, said Dukas, whose firm represents GAMCO Investors Inc. (GBL), founded by Mario Gabelli, Raymond James Financial Inc. (RJF) and other financial-service, asset- management and technology companies but isn't involved in the Fed centennial.
"It has a neutral, authoritative type of feel and doesn't come across as too promotional," he said. It is also a good choice because "a lot of Ron Paul's followers are younger." Paul, a Texas Representative and Republican presidential candidate, has vowed to abolish the Fed.
Bernanke isn't a "flashy" teacher, Blinder said of his former colleague at Princeton, in New Jersey. "Some people get up there and are sort of performers," he said. "Ben does not. He's much more straight-laced. You just hear what's coming out of an incredibly well-ordered mind."
Former students who were interviewed agreed.
"He had this whole vision that he built up over the semester, and at the end you felt you really knew something," said Bryan Caplan, who earned his doctorate in economics at Princeton in 1997 and is now a professor at George Mason University in Fairfax, Virginia.
Door 'Always Open'
"His door was always open, and students could just pop up to chat with him," Ilian Mihov, another former student who is now deputy dean in Singapore at the Insead business school, said in an e-mail. "Outside of the classroom and the school, he was also accessible; every Thanksgiving, we would be generously invited to their place."
Bernanke is "the kind of guy who can check his ego at the door," added Jeffrey Rosensweig, who studied under Bernanke when the Fed chief was a visiting professor at the Massachusetts Institute of Technology in Cambridge.
Rosensweig, who is now an associate professor of finance at Emory University's Goizueta Business School in Atlanta, Georgia, also praised Bernanke for his ability to marry verbal and pictorial class presentations and the abstract with the practical.
Cupcake-Factory Tour
The lectures are the latest effort by the Fed to explain its actions to the public. During the last three years, Bernanke has given television interviews and appeared at town hall-style meetings. He toured a Philadelphia shipyard and a Tasty Baking Co. cupcake factory in 2010 and last year traveled to El Paso, Texas, to speak to soldiers at the military's Fort Bliss. He also began holding press conferences in 2011, after each of the Fed's four two-day policy meetings.
So far, his efforts have had limited success. Twenty-seven percent of Americans viewed Bernanke favorably in a Bloomberg National Poll this month, down from 34 percent a year ago and below Paul's 38 percent rating.
"Middle America may not be a beneficiary of this campaign yet," said Gerry Corbett, head of Redphlag LLC, a San Bruno, California-based communications company, and chairman and chief executive officer of the Public Relations Society of America. "It's a very, very, very long road."
Most of the criticism has been that the Fed is too aggressive in loosening monetary policy, Blinder said. "He's getting a much bigger volume and higher level of vociferousness on that side," and it's "clear which flank he has to protect."
'Treasonous' Threat
Texas Governor Rick Perry, a Republican who was also in the presidential race until Jan. 19, said last year it would be "treasonous" if Bernanke eased policy further.
The Fed has cut short-term interest rates effectively to zero and has suggested it will keep them "exceptionally low" at least through late 2014. It also has undertaken two rounds of bond buying, boosting its balance sheet to $2.9 trillion.
That big portfolio is a "sword of Damocles" hanging over the economy, said Allan Meltzer, a Carnegie Mellon University professor who has written a two-volume history of the Fed. He charged that Bernanke doesn't have a plan for dealing with it, so inflation is headed higher.
"What is the Bernanke policy doing in practice?" Meltzer asked. "It's providing capital to American banks."
Bernanke has defended his record as an inflation fighter by noting that price increases during his six-year tenure as Fed chairman have been below those of his predecessors.
Slower Price Increases
Consumer prices have risen by an average annual 2.4 percent since he took over as chairman in February 2006. That compares with 3.1 percent under Greenspan, chairman from August 1987 through January 2006, and 6.2 percent under Volcker, who headed the central bank in the eight years starting August 1979.
Bernanke has acknowledged the rebound from the deepest recession since the Great Depression has been disappointingly slow, while arguing there are limits to how much the Fed can help. Even though unemployment has fallen from as high as 10 percent in October 2009, it has stalled above 8 percent for 37 months. Gross domestic product rose 1.7 percent last year after a 3 percent increase in 2010.
As long the recovery is lackluster and the jobless rate high, there's just so much Bernanke can do to change the Fed's image, said Eric Dezenhall, co-founder of communications consultant Dezenhall Resources in Washington.
"It's not like if Bernanke did a really good PowerPoint presentation and wore a terrific tie any of this would change," Dezenhall said. "He is not going to accomplish miracles with his fireside chat equivalents. His goal is damage control, not damage elimination."
To contact the reporters on this story: Rich Miller in Washington at rmiller28@bloomberg.net; Joshua Zumbrun in Washington at jzumbrun@bloomberg.net
To contact the editor responsible for this story: Chris Wellisz at cwellisz@bloomberg.net
For Biotech, ‘Fail’ Is Making a Big Comeback {And for Corx, it never left! Nor did the "woe is Corx and the biotech biz" attitude here...}
Published: Monday, 12 Mar 2012 | 3:00 PM ET Text Size
By: Adam Feuerstein
“Fail” is re-entering the lexicon of the biotech investor.
Biotech stocks seemed like they could do no wrong for awhile there, but all hot streaks come to an end eventually, witnessed by a recent string of disappointing clinical trial results and Food and Drug Administration rejections.
Monday, Tranzyme Pharma [TZYM 3.01] announced the failure of a phase III study of ulimorelin, an experimental drug designed to accelerate the gastrointestinal recovery of patients after bowel surgery. Transyme shares plummeted 71 percent to $1.49 in early trading.
Late Friday, Anthera Pharmaceuticals [ANTH 3.59] was forced to halt early a phase III study of its heart drug varespladib. The problem: Varespladib doesn’t work. Anthera shares skidded 55 percent to $2.81 in Monday pre-market trading.
Also Friday, Peregrine Pharmaceuticals [PPHM 0.6416 ] released negative results from a phase II study of its lung cancer drug bavituximab, which was only able to delay tumor growth by 9 days over a control.
These three drug blowups follow closely the setback for Oncothyreon's [ONTY] lung cancer vaccine Stimuvax, which failed to show a significant benefit after a much-hyped interim analysis of a late-stage trial.
The FDA approved a new therapy to improve lung function of premature babies from Discovery Laboratories [DSCO 3.48], but a short-lived pop in the company’s stock price was quickly sold off. FDA also rejected drug applications from NeurogesX [NGSX 0.481 --- UNCH] and Astex Pharmaceuticals [ASTX 1.85 --- UNCH ].
The Nasdaq Biotechnology Index [.NBI 1253.33 --- UNCH] is up 14 percent for the year and still outperforming the broader indexes, but the gap is narrowing. What was an 11 percent margin in mid-February between the NBI and S&P 500 is now down to a 5 percent gap.
Investors are being reminded that drug development is risky, but they are also being bombarded with a glut of new stock issued by biotech and drug companies seeking to raise new cash on the sector's strength. Amylin Pharmaceuticals [AMLN 15.84], Xoma [XOMA 1.88], and Jazz Pharmaceuticals [JAZZ 47.91 --- UNCH] are among companies selling stock to raise cash in recent weeks.
Adding insult to injury, Peregrine filed a new $150 million mixed shelf on the same day it announced the negative bavituximab data. Adventrx Pharmaceuticals [ANX 0.58 --- UNCH], a serial stock diluter with an abysmal drug development track record, signaled its intent to once again hit up investors for more cash. The company filed a $150 million mixed shelf Friday.
Meantime, the flurry of mergers and acquisition activity that began late last year and which launched the biotech sector into overdrive has slowed noticeably. Investors are still waiting to see whether hepatitis C developers Idenix Pharmaceuticals [IDIX 11.37 --- UNCH] and Achillion Pharmaceuticals [ACHN 10.67 --- UNCH] are taken out following similar deals for Pharmasset and Inhibitex.
Where has all the good news in biotech gone?
Wallstarb being 'outed' (#msg-73176265).
A little Friday night humor:
Harold Camping Admits Rapture Prediction 'A Mistake'
By Alexandra Ludka | ABC News – 6 hrs ago
Ninety-year-old Harold Camping predicted that the world would come to an end on May 21, 2011. And then again on October 21, 2011.
And while it has been clear for months that the world, in fact, did not end on either date, Camping has finally issued an official statement admitting the mistake.
According to "When is the Rapture?," an article written by Camping, the Rapture is the end of the world and happens when "our Lord comes to judge the world."
On the day of the Rapture, "the believers in Christ who have not experienced physical death will be changed into their glorified bodies," Camping wrote. "At that time, they will be caught up in the air to be with Christ."
At the time of the first prediction, Camping was the president of Family Radio, a non-profit radio network that, according to its website, acts "with the express purpose of sending the Christian Gospel into the world."
When May 21, 2011 came and went with no sign of the Apocalypse, Camping still said he was not entirely wrong about the prediction. Speaking to the media outside the headquarters of Family Radio on May 23, Camping said that while the world had not ended, the spiritual Rapture had begun.
"We have to be looking at all of this a little bit more spiritual, but it won't be spiritual on Oct. 21," he said. "Because the Bible clearly teaches that then the world is going to be destroyed altogether."
Shortly after he said that, Camping suffered a stroke on June 13, 2011, and retired from Family Radio.
When Oct. 21 also came and went with no sign of the Rapture, Camping was publicly silent until now.
"We humbly acknowledge we were wrong about the timing," his statement reads. "We tremble before God as we humbly ask Him for forgiveness for making that sinful statement."
But Camping and Family Radio say they believe that while the prediction was a mistake, it was all in God's plan.
"Though we were wrong God is still using the May 21 warning in a very mighty way. In the months following May 21 the Bible has, in some ways, come out from under the shadows and is now being discussed by all kinds of people who never before paid any attention to the Bible," Camping wrote. "Even as God used sinful Balaam to accomplish His purposes, so He used our sin to accomplish His purpose of making the whole world acquainted with the Bible."
And, the statement reads, Family Radio will not announce a new prediction for the end of the world.
"We also openly acknowledge that we have no new evidence pointing to another date for the end of the world. Though many dates are circulating, Family Radio has no interest in even considering another date. God has humbled us through the events of May 21, to continue to even more fervently search the Scriptures (the Bible), not to find dates, but to be more faithful in our understanding."
Ombow-Do you know this guy?:
Delray Beach jazz trumpeter Lou Colombo, 84, dies
By Phillip Valys, Staff Writer
7:55 p.m. EST, March 5, 2012
Lou Colombo, a swinging South Florida jazzman known for his one-handed trumpeting prowess and stints performing alongside the likes of Dizzy Gillespie, Tony Bennett and Mel Torme, died Saturday night in a car crash outside his daughter's restaurant in Fort Myers.
The 84-year-old part-time Delray Beach resident divided his time between Cape Cod in the summer and Florida in the winter. Colombo had just finished playing a gig at The Roadhouse Café on when the accident occured, said his daughter, Lynda Colombo.
"He had this new trumpet mouthpiece he had liked the sound of, and he called Mom in a voicemail just before the crash to say he had an incredible set," Lynda Colombo said, her voice choking. "My dad is a perfectionist, so he never thinks he plays great. But we all do. Everybody does."
During his 70-odd years as a musician, the jazzman was never far from a brass instrument, not even during stints with minor-league baseball clubs of the St. Louis Cardinals and the Brooklyn Dodgers in the 1940s. After an ankle injury sidelined his baseball career, he took up trumpeting full-time.
"His horn was an extension of his body, and that's where he was most comfortable, that's how he could express himself," Colombo said.
When in South Florida Colombo would call Boca resident Richard Oakley to play shows. The trombonist and flugel horn player went gigging everywhere with Colombo, from juke joints to The Marriott Hotel to the St. Andrews and Boca Greens country clubs.
"He was just a marvelous man who always pushed the gas pedal for Dixieland jazz," said Oakley, 79, who last performed with Colombo six months ago. "We'd play twos and fours against each other — it was a lot of good old time goodness. It was a just a big frat party."
Colombo's unusual playing style even once courted attention from jazz giant Dizzy Gillespie, who heaped praise on Colombo in a 1988 radio interview: "Lou's a beautiful player. He plays the valves with his right hand but doesn't hold the horn with his left hand. I've been preaching his name ever since that night I first heard him down on Cape Cod."
Mari Mennel Bell, a Fort Lauderdale pianist and an admitted "groupie," said she last saw Colombo play during his regular Monday night gig last week at Pa'DeGennaro's in Lauderdale-by-the-Sea, and would often criss-cross the state to catch his regular Thursday night show at The Roadhouse Café in Fort Myers.
"Lou was 100-percent gentleman, and he was such an entertainer. The one-handed way he played created this very casual atmosphere," she said. "He touched everyone's hearts. You felt like he was performing just for you."
Colombo is survived by his wife, Noelle, six children, nine grandchildren and two great-grandchildren. His family plans to hold a private memorial later this week in Cape Cod.
What Ampacan't do, Enkam can:
Peptide Sparks Synaptic Plasticity, Improves Memory in Rodents
24 February 2012. A small peptide called FGL boosts learning and memory when administered to rodents, and is poised to begin clinical trials in Alzheimer’s disease patients this year. Intriguingly, FGL sharpens memory in wild-type rats as well as in several disease models. While prior studies suggested that the heightened learning resulted from improved synaptic plasticity in the hippocampus (see Dallérac et al., 2011), the mechanism was unclear. Now, in the February 21 PLoS Biology, researchers led by José Esteban at the Universidad Autónoma de Madrid, Spain, detail the signaling pathway behind this effect. They report that FGL treatment stimulates activity-dependent delivery of glutamate receptors to synapses, leading to a long-term enhancement of synaptic transmission.
Scientists contacted by Alzforum expressed enthusiasm for the findings. “The effect on synaptic transmission is impressive, and represents the only peptide that I know of that is capable of enhancing transmission and plasticity,” wrote Roberto Malinow at the University of California, San Diego.
Elisabeth Bock and colleagues at the University of Copenhagen, Denmark, designed the 15-amino-acid peptide in 2004, basing it on a portion of neural cell adhesion molecule (NCAM). NCAM is known to play a role in synaptic plasticity (see, e.g., Dityatev et al., 2000). Bock and colleagues showed that the FG loop (FGL) from the second fibronectin type III module of NCAM binds and activates fibroblast growth factor receptor 1 (FGFR1) (see Kiselyov et al., 2003). The FGL peptide mimics this activity and improves cell survival in primary neuronal cultures exposed to toxins, the authors reported (see Neiiendam et al., 2004). Moreover, FGL injected subcutaneously into wild-type rats crosses the blood-brain barrier and enhances several forms of memory, including fear conditioning, social and motor learning, and spatial memory tested in the Morris water maze (see Cambon et al., 2004; Secher et al., 2006). Enhanced spatial memory persists for as long as two weeks after peptide administration. Furthermore, treated rats behave normally in an open field test, suggesting the peptide does not increase anxiety. Behavioral and social problems often accompany changes in learning, said Philip Washbourne from the University of Oregon, Eugene.
Esteban and colleagues wanted to dissect the mechanisms behind FGL’s effects. Joint first authors Shira Knafo and César Venero treated hippocampal slice cultures with 10 µg/ml FGL for 24 hours, then removed FGL for a day before electrophysiological testing. Peptide treatment heightened AMPA receptor-mediated transmission at excitatory CA1 synapses, which the authors showed was due to insertion of additional AMPA receptors. Inhibiting protein kinase C (PKC), a downstream effector of the FGF1 receptor, eliminated the AMPA receptor influx. To demonstrate that the same mechanism occurs in vivo, the authors administered both FGL and the PKC inhibitor into rat brains through a cannula, and found that the inhibitor abolished FGL-mediated memory enhancement.
Importantly, enhanced synaptic transmission does not occur spontaneously after FGL treatment. Instead, the peptide seems to facilitate long-term potentiation (LTP) in response to synaptic activity. In FGL-treated hippocampal slices, electrical stimulation induced LTP nearly twice as strongly as in untreated slices, and inhibiting PKC prevented this effect. Furthermore, when the authors blocked NMDA receptors, which are crucial for LTP, FGL treatment no longer pumped up AMPA receptor delivery. Esteban notes that this activity dependence is critical for a cognitive enhancer. If the peptide indiscriminately increased synaptic transmission, it might overexcite neurons and lead to epilepsy, he said. But by heightening synaptic plasticity only in response to activity, the peptide helps the animal encode information more easily, leading to better memory.
“I find it intriguing that memory processes can be improved over normal levels,” Esteban told Alzforum. This implies that the human memory system is not running at the top of its possible performance, he said. Esteban pointed out that FGL recruits physiological memory mechanisms, which suggests that the peptide may have few side effects. It also may not need to be given chronically. Esteban and colleagues found that PKC, as well as other proteins involved in LTP, stays activated for at least 24 hours after FGL removal. The peptide therefore provides a long-lasting augmentation of synaptic plasticity, in agreement with in-vivo results. “We still don’t know what allows the system to stay in this sensitized state,” Esteban noted.
In addition to looking at electrophysiology, the authors examined the structure of dendritic spines in the CA1 region. However, they found no evidence that FGL increased spine density or changed spine shape. Previous studies have also reported no change in spine density after FGL treatment, although earlier work did show evidence of alterations in fine structure (see Popov et al., 2008).
“The synaptic plasticity mediated by the FGL agonist, therefore, would appear to relate to retuning the strength of existing cell synapses,” rather than to creating new synapses, Ciaran Regan at University College Dublin, Ireland, wrote to Alzforum. This implies the peptide may be most effective for treating conditions where synaptic transmission may be weakened or perturbed, for example, in depression, rather than disorders such as AD, where synapses are lost, Regan suggested (see full comment below).
Other commentators expressed enthusiasm about the therapeutic potential of the peptide, while noting some cautions. Washbourne pointed out that it will be important to do more extensive behavioral tests, in particular, looking for effects of FGL on social behavior, before taking the peptide to clinical trials. Paul Lombroso at Yale University, New Haven, Connecticut, suggested the peptide might have broad applicability for numerous types of cognitive dysfunction, telling Alzforum, “I think this is an excellent paper, and very exciting in terms of our attempts to find reagents that may improve cognitive deficits.”
So far, FGL has been shown to enhance memory or protect neurons in animal models of chronic stress (see Borcel et al., 2008 and Bisaz et al., 2011), depression (see Aonurm-Helm et al., 2008), ischemia (see Skibo et al., 2005), and traumatic brain injury (see Pedersen et al., 2008). Other studies indicate that the peptide reduces neuroinflammation (see Downer et al., 2009 and Ojo et al., 2011). FGL has also been found to prevent age-related structural changes in synapses (see Ojo et al., 2011).
Does the peptide hold potential for treating Alzheimer’s disease? One published study from Bock’s group suggests it does. Rats injected with Aß oligomers develop signs of AD-like neuropathology and failing memory, but when also given FGL, either subcutaneously or intranasally, these deficits do not develop. In addition, Aß-injected rats having more advanced pathology improved after FGL treatment, showing fewer amyloid plaques and better memory than untreated controls (see Klementiev et al., 2007). Experiments in rats, dogs, and monkeys found no toxic effects from the peptide, and an eight-day human study on 24 healthy male volunteers revealed no ill effects from a single dose of FGL given intranasally (see Anand et al., 2007). Based on these data, Enkam Pharmaceuticals, a biotechnology company based in Copenhagen, Denmark, plans to begin clinical trials of a modified form of FGL in 2012 (see company press release). In cooperation with a consortium of companies, universities, and AD patient groups, Enkam will lead three Phase 1 safety studies, one Phase 2a study in AD patients, and also a pilot study in stroke patients. The consortium has been awarded a €6 million grant from the European Union’s Seventh Framework Programme to conduct these studies (see also ARF related news story).—Madolyn Bowman Rogers.
Reference:
Knafo S, Venero C, Sánchez-Puelles C, Pereda-Peréz I, Franco A, Sandi C, Suárez LM, Solís JM, Alonso-Nanclares L, Martín ED, Merino-Serrais P, Borcel E, Li S, Chen Y, Gonzalez-Soriano J, Berezin V, Bock E, DeFelipe J, Esteban JA. Facilitation of AMPA receptor synaptic delivery as a molecular mechanism for cognitive enhancement. PLoS Biol. 2012 Feb;10(2):e1001262.
Comments on News and Primary Papers
Comment by: Ciaran Regan
Submitted 24 February 2012
These studies explore the cognition-enhancing actions of a peptide agonist of the neural cell adhesion molecule (NCAM), the FG loop (FGL) peptide, synthesized from the second fibronectin type III module of NCAM. The identification of FGL as a cognition-enhancing agent is well established in the literature, and this new and most comprehensive dataset now provides further information on the molecular mechanisms by which this peptide may mediate its action. The bottom line outcome of these studies is that FGL enhances cognition in rodents and long-term potentiation (LTP), a cellular model of memory and learning, in hippocampal slices. This facilitation is demonstrated to be mediated by FGL enhancing the delivery of AMPA-type glutamate receptor into excitatory synapses following activation of NMDA-type glutamate receptors. Importantly, these effects are reported to be specifically mediated by PKC activation.
This new dataset opens up pathways (literally) to further experiments such as the effect of the FGL peptide on the polysialylation status of NCAM, which also regulates...
That's outside his realm of expertise, presumably that of neurology and psychology. He is the first to point that out. He also is a major apologist for the great mgmt of Cortex, so the 'woe is we' card doesn't work for me. With no precedent or standard template for an advanced RD study, you have a free ticket to set the standard for the present and future of RD trials. Are these guys robot pigs or exceptionalists? Isn't it obvious.
Why should Cortex end any differently than has been their M.O. over the years? And if so, how would this anomaly (going out in a blaze) play out? I wouldn't expect much no matter how hard they try. Cortex mgmt gives a whole new meaning to the term 'success'. Their success can only be dubbed 'ironic success'.
Astonishing to me is something that would benefit the shareholders and company. If the industry doesn't react, there is nothing astonishing about it. Especially after this much time having elapsed. The fluke/delayed reaction window of vindication closed a long time ago...
Calling those results "astonishing" only proves (if accurate), to an exponential degree, the abysmal failure the mgmt has been; weak industry, bad economy, bad luck, poor advice, and poor regulations included.
I guess I will give you some tentative credibility that there was something awesome in those studies; I just provided a justifiable/valid reason why such "amazing" data has led to more failure.
Your problem is that your arguments lack a balanced perspective. Even Ombow told you that years ago.
Yes, gfp, I like to stir the pot. I do it sometimes when the crap coagulates at the surface. To put it another way: when the nonsensometer violates the redzone for too long or too extremely, I get out my wooden spoon and whip it up :)
I'm not trying to silence anyone, just calling people out on their own remarks in an effort to help them. We all need to get a grip from time to time. I would like to encourage holycow to keep posting, albeit with more sense, as long as they don't shut down the internet (lol).
You're misreading my posts like you misread the future. I'm not hostile, bigword. I just like to have fun at the expense of people who think they know, but they don't. Your disingenuous reply notwithstanding. Having skimmed through some of your (and holycrap's) early Cytogenix posts (after your defensive presumptions towards me), I see a potential for much more fodder :) I read your posts, obviously. You can't tell me you're not hostile. As long as Obama's in the WH especially (likely another 4 years), I'm sure you will continue to act out your contempt of the markets by projecting your hate on our leader. The irony is, he has been a pillar of stability for our economy, never mind the means to reach that end. I'm conflicted regarding my opinion of his moves, I admit it. But I am not going to bash his accomplishments having been somewhat a beneficiary of them.
The funny thing is, I agree with much of what you say. The systems (political and capital) are broken, and irresponsible and reckless mentality is to blame. I just take exception to your exaggerations, embellishments, and pretentious innuendo. However, I'm not angry with you (or your little followers), to the contrary, I find it hysterical.
So...go to hell, bigtalker :)
They may be small; they may be silent; but they are anything but magical.
Holydumbshit-Quit the charade. It makes no sense that you post here just to praise bigwriter, yet contradict all his suggestions and advice. You are nothing more than a strawman puppet--a set-up man--whose sole purpose is to make little bigboy who cried wolf seem a little more intelligent and sagacious. From Wikipedia:
The three C's: Cephalon, Cortex, and Corcept. Make it a fourth for 'Curse' (#msg-23705284):
Corcept Therapeutics Incorporated Announces FDA Approval of Korlym(TM) (Mifepristone): First and Only Approved Medication for Cushing's Syndrome Patients
Press Release: Corcept Therapeutics –
MENLO PARK, CA--(Marketwire -02/17/12)- Corcept Therapeutics Incorporated (NASDAQ: CORT - News) announced today that the U.S. Food and Drug Administration (FDA) has approved Korlym™ (mifepristone 300 mg tablets) as a once-daily oral medicine to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have diabetes mellitus type 2 or glucose intolerance and have failed surgery or are not candidates for surgery.
"We appreciate the FDA's diligent attention to our NDA and its grant of approval on the PDUFA date," said Joseph K. Belanoff, M.D., the company's Chief Executive Officer. "We plan to make Korlym available to patients by May 1 through a distribution system designed to support both patients and prescribers."
Corcept will be the sole marketer of Korlym. "A relatively small number of endocrinologists regularly treat patients with Cushing's syndrome," added Dr. Belanoff. "These doctors can be reached without a large sales and marketing infrastructure." The company has begun hiring Medical Science Liaisons to inform practitioners about the drug, which will be dispensed by the leading specialty pharmacy company CuraScript SP, a subsidiary of Express Scripts.
"Korlym is a significant advance in the treatment of patients suffering from the debilitating symptoms of Cushing's syndrome," said Robert L. Roe, M.D., Corcept's President. "For the first time, these patients have access to an approved therapy when surgery has failed or is not an option."
Korlym clinical trial investigator Amir Hamrahian, M.D., Department of Endocrinology, Diabetes and Metabolism at the Cleveland Clinic said, "There are not many effective treatment options for patients with Cushing's syndrome. Although surgery is standard first line treatment for the disease, it is not always successful and not all patients are candidates. As part of the clinical trial, I have used Korlym successfully and my patients continue to do well on the medicine. I'm excited to be able to continue using Korlym in these patients and others who need it. This medicine's approval gives me a much needed tool to better treat patients."
Dr. Hamrahian's comments were seconded by Maureen V., a patient in Corcept's Phase 3 clinical trial: "I had pituitary surgery to treat my Cushing's syndrome. Unfortunately, my surgery wasn't successful. I was lucky to get into the study and get Korlym treatment. I have been taking the medicine successfully for over a year, and I am extremely happy that it was approved by the FDA. Now I know I'll be able to keep taking it. It has made a big difference in my life."
Clinical Trial Results Supporting FDA Approval
The clinical data supporting the FDA approval of Korlym resulted from an uncontrolled, open-label, multi-center, 24-week phase III study of 50 patients who had endogenous Cushing's syndrome and were either not eligible for or had relapsed from surgery and were either glucose intolerant (29 patients) or had hypertension (21 patients). Within the glucose intolerant group, 60 percent of patients had a greater than 25 percent reduction from baseline in the area under the curve in the oral glucose tolerance test. In this group, mean hemoglobin A1C (HbA1C) was reduced from 7.4 percent to 6.3 percent. All 14 patients with above-normal HbA1C levels at baseline experienced reductions. Eight of these 14 normalized their HbA1C. Antidiabetic medications were reduced in seven of the 15 patients with diabetes mellitus type 2 and remained constant in the others.
Patients who responded to therapy were allowed enrollment in an extension trial. Eighty-eight percent of the patients who completed the trial chose to do so.
A peer-reviewed analysis of the study results will soon be published in a leading journal.
Patients in the study started Korlym treatment on a dose of 300 mg administered once daily. Their dose was then titrated to maximum clinical effect. As indicated in the medicine's label, physicians prescribing Korlym may determine the appropriate dose for each patient by assessing tolerability and degree of improvement in Cushing's syndrome manifestations. In the first six weeks, these manifestations may include changes in glucose control, anti-diabetic medication requirements, insulin levels and psychiatric symptoms. After two months, assessment may also be based on improvements in cushingoid appearance, acne, hirsutism, striae, decreased body weight, along with further changes in glucose control.
About Korlym™ (mifepristone 300 mg tablets)
Korlym is a once-daily oral medication that blocks the glucocorticoid receptor type II (GR-II) to which cortisol normally binds. By blocking this receptor, Korlym inhibits the effects of excess cortisol in Cushing's syndrome patients.
The FDA has designated Korlym as an Orphan Drug for treatment of the clinical manifestations of endogenous Cushing's syndrome. Orphan Drug designation is a special status designed to encourage the development of medicines for rare diseases and conditions. Because Korlym is an Orphan Drug, Corcept will have marketing exclusivity consistent with the FDA's designation until February 2019.
About Cushing's Syndrome
Endogenous Cushing's syndrome is a rare and life-threatening endocrine disorder that results from long-term exposure to excess levels of the hormone cortisol. This excess is caused by tumors that usually occur in the pituitary or adrenal glands that over-produce, or prompt the over-production of, cortisol.
Although cortisol at normal levels is essential to health, in excess it causes a variety of problems, including hyperglycemia, upper body obesity, a rounded face, stretch marks on the skin, an accumulation of fat on the back, thin and easily bruised skin, muscle weakness, bone weakness, persistent infections, high blood pressure, fatigue, irritability, anxiety, psychosis and depression. Women may have menstrual irregularities and facial hair growth, while men may have decreased fertility or erectile dysfunction. More than 70 percent of Cushing's syndrome patients suffer from glucose intolerance or diabetes.
The treatment of an endogenous Cushing's syndrome patient depends on the cause. The first-line approach is surgery to remove the tumor. If surgery is not successful or is not an option, radiation may be used, but that therapy can take up to ten years to achieve full effect. Surgery and radiation are successful in only approximately one-half of all cases.
If left untreated, Cushing's syndrome has a five-year mortality rate of 50 percent.
An orphan disease, Cushing's syndrome occurs in about 20,000 people in the United States, mostly women between the ages of 20 and 50.
Conference Call Information
Corcept will hold a conference call on Tuesday, February 21, 2012 at 9:00 a.m. Eastern Time (6:00 a.m. Pacific Time) to discuss this announcement. To participate in the live call please dial 1-800-264-7882 from the United States or +1-847-413-3708 internationally. The pass code is 31838602. Please dial in approximately 10 minutes before the start of the call.
A replay of the conference call will be available through March 6, 2012 at 1-888-843-7419 from the United States and +1-630-652-3042 internationally. The pass code is 31838602.
IMPORTANT SAFETY INFORMATION
WARNING: TERMINATION OF PREGNANCY
See full prescribing information for complete boxed warning.
Mifepristone has potent antiprogestational effects and will result in the termination of pregnancy. Pregnancy must therefore be excluded before the initiation of treatment with Korlym, or if treatment is interrupted for more than 14 days in females of reproductive potential.
Contraindications
Pregnancy
Use of simvastatin or lovastatin and CYP 3A substrates with narrow therapeutic range
Concurrent long-term corticosteroid use
Women with history of unexplained vaginal bleeding
Women with endometrial hyperplasia with atypia or endometrial carcinoma
Warnings and Precautions
Adrenal insufficiency: Patients should be closely monitored for signs and symptoms of adrenal insufficiency.
Hypokalemia: Hypokalemia should be corrected prior to treatment and monitored for during treatment.
Vaginal bleeding and endometrial changes: Women may experience endometrial thickening or unexpected vaginal bleeding. Use with caution if patient also has a hemorrhagic disorder or is on anti-coagulant therapy.
QT interval prolongation: Avoid use with QT interval-prolonging drugs, or in patients with potassium channel variants resulting in a long QT interval.
Use of Strong CYP3A Inhibitors: Concomitant use can increase mifepristone plasma levels significantly. Use only when necessary and limit mifepristone dose to 300 mg.
Adverse Reactions
Most common adverse reactions in Cushing's syndrome (= 20%): nausea, fatigue, headache, decreased blood potassium, arthralgia, vomiting, peripheral edema, hypertension, dizziness, decreased appetite, endometrial hypertrophy.
To report suspected adverse reactions, contact Corcept Therapeutics at 1-855-844-3270 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Drug Interactions
Drugs metabolized by CYP3A: Administer drugs that are metabolized by CYP3A at the lowest dose when used with Korlym.
CYP3A inhibitors: Caution should be used when Korlym is used with strong CYP3A inhibitors. Limit mifepristone dose to 300 mg per day when used with strong CYP3A inhibitors.
CYP3A inducers: Do not use Korlym with CYP3A inducers.
Drugs metabolized by CYP2C8/2C9: Use the lowest dose of CYP2C8/2C9 substrates when used with Korlym.
Drugs metabolized by CYP2B6: Use of Korlym should be done with caution with bupropion and efavirenz.
Hormonal contraceptives: Do not use with Korlym.
Use in Specific Populations
Nursing mothers: Discontinue drug or discontinue nursing.
Please see the accompanying full Prescribing Information including boxed warning at www.corcept.com/prescribinginfo.pdf
Please see the accompanying Medication Guide at www.corcept.com/medicationguide.pdf
About Corcept Therapeutics Incorporated
Corcept is a pharmaceutical company engaged in the discovery, development and commercialization of drugs for the treatment of severe metabolic and psychiatric disorders. Korlym, a first generation GR-II antagonist, is the company's first FDA-approved medication. The company has a portfolio of new selective GR-II antagonists that block the effects of cortisol but not progesterone. Corcept also owns an extensive intellectual property portfolio covering the use of GR-II antagonists, including mifepristone, in the treatment of a wide variety of psychiatric and metabolic disorders. The company also holds composition of matter patents for its selective GR-II antagonists.
Statements made in this news release, other than statements of historical fact, are forward-looking statements. Forward-looking statements are subject to a number of known and unknown risks and uncertainties that might cause actual results to differ materially from those expressed or implied by such statements. For example, there can be no assurances that clinical results will be predictive of real-world use, or regarding the pace of Korlym's acceptance by physicians and patients, the reimbursement decisions of government or private insurance payers, the effects of rapid technological change and competition, the protections afforded by Korlym's Orphan Drug Designation or by Corcept's other intellectual property rights, and the cost, pace and success of Corcept's other product development efforts. These and other risks are set forth in the Company's SEC filings, all of which are available from our website (www.corcept.com) or from the SEC's website (www.sec.gov). We disclaim any intention or duty to update any forward-looking statement made in this news release.
This Is Your Brain on a Hot Streak (courtesy of hptaxis on Biotech Values Board):
By JASON ZWEIG
Past returns are no guarantee of future success. Just like smokers ignoring the Surgeon General's warning on the side of cigarette packs, investors overlook the most obvious caution about the stock market at their peril.
Even after Friday's stumble over renewed fears about Europe, the Standard & Poor's 500-stock index has gained 7% so far this year, and the Russell 2000 small-stock index is up 11%.
Why is it so hard for investors to regard such short-term hot streaks with the cold eye they deserve?
Decision Research, a nonprofit think tank in Eugene, Ore., has conducted a nationwide online survey of investors seven times since 2008. These surveys have shown that investors' forecasts of future returns go up after the market has risen and down after it has fallen.
William Burns, an analyst at Decision Research, says investors' forecasts of the market's return over the coming year were heavily swayed by how stocks performed in the previous month.
They might not have had a choice. The investing mind comes with built-in machinery that sizes up the future based on a surprisingly short sample of the past. Neuroscientists say the human brain probably evolved this response in a simple environment in which the cues to basic payoffs like food and shelter changed slowly and rarely, making the latest signals most valuable—nothing like what today's investors face with electronic markets in a constant state of flux.
Experiments led by neuroscientist Paul Glimcher of New York University found that cells deep in the brain calculate a sort of moving average of past events, giving the greatest weight to the most recent outcomes.
When the latest rewards turn out to be better than the long-term pattern, these neurons fire unusually quickly, spreading a burst of dopamine—the neurotransmitter that triggers the pursuit of reward—throughout the brain.
Thus, after a decade of mostly dismal stock returns, even a month or two of outperformance might prompt you into an impulsive plunge back toward stocks.
Some investors seem to have learned how to resist this tendency, and you should, too.
Charles Manski, an economist at Northwestern University, has analyzed how people form expectations of what the stock market will do next. Based on nationwide surveys of households conducted from 1999 through 2004, he has identified three main types of amateur forecasters.
Just over 40%—the largest group—believe recent performance is likely to persist. Another third of investors think recent returns are likely to reverse. Finally, roughly one-quarter of people think returns are random and essentially unpredictable.
But each of these attitudes carries a distinctive kind of risk.
Investors who believe returns are unpredictable should, in the long run, capture the general rise in stock values that patient investors have generally received in the past. But, in the short run, they won't sidestep a big drop in the market.
Investors who believe recent returns are ripe for a reversal can sell too soon in a bull market and buy before a bear market hits bottom.
Those who think recent returns will persist are especially prone to error. If you think a hot market is likely to get hotter, you will have no qualms about buying high; if you believe a bad market is bound to get even worse, you will end up selling low.
Here are a couple of steps you can take to minimize your odds of ramping up your exposure to stocks as their prices rise.
First, think back to the last time you felt certain you knew where the market was headed. Were you sure, at the beginning of 2011, that interest rates had to start rising soon? Were you convinced, in March 2009, that stocks were bound to keep dropping? The mere act of pausing to ask yourself how reliable your intuitions are might be enough to make you recognize that you need better justifications before you take action.
Then force yourself to come up with several solid reasons why the U.S. stock market is undervalued enough to justify suddenly increasing your exposure to it. And no cheating: You can't use "because it's been going up lately" as one of your reasons. While you are at it, think of a few factors that might make stocks stop going up.
Write down your reasons, so you can look back later and review your logic. The best way to learn from your forecasts—right or wrong—is to track them over time.
None of this means you shouldn't own stocks. It simply means you shouldn't rush into buying more just because the market has had a flashy rise.
Decisions made in haste usually turn out to be mistakes—and big decisions made in haste almost always turn out to be big mistakes.
— intelligentinvestor@wsj.com; twitter.com/jasonzweigwsj
China Secrets Case Yields Indictment
http://online.wsj.com/article/SB10001424052970203315804577211463864126278.html
By JUSTIN SCHECK
SAN FRANCISCO—A federal grand jury on Wednesday indicted a San Francisco Bay area couple on charges of conspiring to steal trade secrets from DuPont Co. and sell them to Chinese state-owned companies.
The indictment said Walter Liew, 54 years old, and his wife, Christina Liew, 49, conspired to take confidential DuPont documents and used them to obtain more than $20 million in contracts from companies in China.
The case is the latest in a series of federal indictments alleging the theft of U.S. companies' intellectual property by Chinese companies.
On Wednesday, a federal court in Chicago convicted Chinese national Hanjuan Jin of stealing trade secrets from Motorola Inc. but acquitted her of more serious espionage charges. Federal prosecutors in 2010 abandoned a corporate-espionage case against two men accused of stealing secrets from NetLogic Microsystems Inc. to sell to Chinese companies after a jury acquitted the men on some charges and deadlocked on others.
The indictment against the Liews came after nearly a yearlong investigation in which a witness committed suicide and federal authorities detained two Chinese executives for weeks as witnesses, people familiar with the matter said.
The indictment alleged that Mr. Liew gained information on DuPont's titanium-manufacturing practices by hiring former DuPont employees with knowledge of the company's technology.
A DuPont spokesman said the Wilmington, Del., company approached law-enforcement officials after learning that information on its titanium-dioxide factories had been stolen. Titanium dioxide is found in paints with military and aerospace uses, among other things. DuPont has filed a civil suit against Mr. Liew that is pending.
Lawyers for the Liews declined to comment on Wednesday's indictment.
Ling-Chi Wang, a professor emeritus at University of California, Berkeley, who has been advising the Liews on how to fight the charges, said he was "outraged" that prosecutors detained Mr. Liew, a U.S. citizen, for seven months before obtaining the indictment.
The investigation gained steam over the summer, prosecutors said in court documents, after FBI agents arrested the Liews on charges of obstructing justice after they tried to keep agents from a trove of documents during a search of their home. The Liews have pleaded not guilty to the obstruction charges.
The documents, which prosecutors filed in court last week, include letters and emails in which Mr. Liew allegedly wrote that a Chinese government official told him to develop expertise in titanium manufacturing and wrote that he has "possession and mastery of the DuPont titanium" technology that he can sell to Chinese companies.
Mr. Liew's lawyer has said in court filings that the documents aren't accurate.
In a statement, China's Ministry of Commerce said it hasn't "heard from the U.S. government or relevant industrial circles about the issue," and said the "Chinese government has long been putting emphasis on the protection of Intellectual property."
Prosecutors also built their case using business associates of the Liews, the people familiar with the matter said. These included two executives from Pangang Group Co., a state-owned Chinese enterprise that is a defendant in the case, who federal agents detained last year and prevented from leaving the U.S. to obtain testimony about the Liews, the people said. The executives, the people said, recently were allowed to return to China.
Pangang, which was named as a defendant in the indictment, couldn't be reached for comment. The indictment also names four other Chinese state-owned companies and three business associates of the Liews as defendants.
A former employee of Mr. Liew, Reno, Nev., engineer Tim Spitler, told prosecutors he discussed secret DuPont documents with Mr. Liew, people familiar with the investigation said. Mr. Spitler was expected to be a witness for the government but killed himself last month, the people said. Members of his family didn't return calls.
Wednesday's indictment said Mr. Liew's attempts to obtain and sell DuPont secrets began in the 1990s, when Chinese-government officials placed a priority on the development of titanium-dioxide manufacturing.
In 1998, the indictment said, Mr. Liew signed a $5.6 million contract to sell the technology to a Chinese company, and he signed larger deals with other companies in 2005 and 2009. From 2003 to 2008, prosecutors alleged, Mr. Liew and his associates advised Pangang Group on constructing a titanium-manufacturing plan that used DuPont blueprints.
—Yoli Zhang contributed
to this article.
Write to Justin Scheck at justin.scheck@wsj.com
OT-The flawless catch by Manningham on the Giants' last drive was something to behold: Simply divine! The giant David wins!
Ps. It takes a Bold Eagle [fan] to prefer a Giant victory...
Metals: In Sickness and in Health
http://www.livescience.com/18247-metals-human-body-health-nigms.html
Stephanie Dutchen, National Institutes of Health
01 February 2012
We're not quite Iron Man, but metals are intricately entwined with our bodies. They make vital functions like respiration, circulation and reproduction possible.
Cobalt, for instance, found at the core of vitamin B12, is key to making red blood cells, while iron allows those cells to ferry oxygen and other important chemicals to the body's tissues. Calcium not only strengthens bones but also plays a role in muscle, nerve function and blood clotting. Sodium and potassium help the heart and nerves communicate through electrical signals.
As the mercury-tainted Mad Hatter and headlines about lead poisoning attest, exposure to too much metal can be harmful. But not getting enough metal in the right places can make us sick, too. This is the case with conditions such as iron-deficiency anemia and osteoporosis. Read on to find out about National Institutes of Health-funded research into two metals that affect our health in unexpected ways.
Zinc imbalance
Small amounts of zinc help ensure a proper immune response and healthy nervous system. Zinc also regulates the function of some genes, enables many proteins to carry out their vital roles and helps speed the chemical reactions that keep us alive. On the flip side, an imbalance of zinc has been linked to Alzheimer's disease, diabetes, prostate cancer and seizures.
Chemist Stephen Lippard of the Massachusetts Institute of Technology, who previously developed fluorescent chemical sensors that detect tiny amounts of zinc in the body, discovered with colleagues that zinc helps regulate communication between two types of brain cells in the hippocampus, the brain's center of learning and memory. Their findings suggest that zinc affects how we form memories and that high concentrations may contribute to epilepsy, where abnormal cell communication causes seizures. Scientists had seen zinc in specific hippocampal cells before but weren't sure what it did there.
Chaperoning copper
Our bodies take great care to make sure metals go only where they need to and in exactly the right amount. Like teachers keeping an eye on students at the prom, so-called "chaperone" proteins protect metals (and the cell) from unwanted interactions while they safely deliver them to their cellular destinations. Problems can arise if chaperones don't do their jobs properly.
Take copper as an example. Malfunctioning chaperones that starve proteins of copper can lead to weak limbs, bone growths, seizures and kinky, brittle hair. That's what happens in people with Menkes syndrome. Copper that gets shut out of cells can accumulate in the bloodstream and cause a different disorder, Wilson's disease. High levels of copper can cause liver damage, kidney failure, coma and death. A copper chaperone that also ferries platinum can affect how cancer patients respond to cisplatin, a platinum-containing substance used in drugs to treat advanced testicular and ovarian cancers.
One way researchers are studying these copper-related disorders is by looking at the three-dimensional shapes of the chaperones. For instance, researchers at Northwestern University deciphered the intricate structure of a chaperone that inserts a molecule of copper into an enzyme whose defective forms have been linked to some inherited types of amyotrophic lateral sclerosis, also known as Lou Gehrig's disease. This structural knowledge, which offers insight into how the chaperone works and interacts with other molecules, deepens scientists' understanding of the disease and could provide a potential new treatment target.
Your welcome, Gfp. I have been contemplating a small investment for some time. Unlike Cortex, they have raised plenty of money from many sources in the last couple years. Their unique approach; the efficacy they have shown (although on a small scale); the attention they have garnered in the field; the safety profile (so far); and, the rather small market cap, gives this risky investment some explosive potential.
If something else falls into their lap -- as the RD discovery did -- I would get out before the existing mgmt has enough opportunity to squander it.
At this point in the disaster known as Cortex, I hardly fault mgmt (per se): It is the worthless enablers in and just outside the organization whom deserve the credit (ie, BOD, large shareholders, industry proponents, passive participants). Yes, I blame myself for 'staying the course' through this real-life nightmare.
With memories like these, who needs Ampakines (lol)!
Tau Joins APP in the Ironworks
http://www.alzforum.org/new/detail.asp?id=3052
3 February 2012. Mutations in tau fan the flames of Alzheimer’s, Parkinson’s, and other tauopathies. What is tau doing that gets it mixed up in so many neurodegenerative conditions? Could the answer lie not in the tangles that besmirch the brains of affected individuals, but in tau’s failure to perform a newly discovered role: promoting iron export? Ashley Bush and colleagues at the University of Melbourne in Australia report in the January 29 Nature Medicine online that without tau, amyloid precursor protein (APP) is unable to reach neurons’ surfaces, where it is needed to work the bellows that pump excess iron out of the cell. Mice missing tau develop symptoms akin to the Parkinson’s-dementia complex that afflicts many people with PD, Bush said. A gentle chelator that sops up the extra iron cures them, suggesting a potential route to treat not only Parkinson’s, but also Alzheimer’s and other conditions, Bush claims.
Tau is a microtubule-binding protein believed to support axonal traffic—but researchers are not sure what kind of cargo might be most important. “We think it is APP,” Bush said. “We feel this is the strongest evidence that the problem [in Parkinson’s] is the loss of iron homeostasis.” Cells need iron, but not too much since it can participate in the formation of dangerous free radicals. Iron is also found in amyloid plaques and tau tangles (Smith et al., 1997). Bush has been chasing the question of metal malfunction in neurodegeneration for years, systematically scouring Alzheimer’s proteins for a potential role in metal management. His group implicated presenilins in cellular uptake of zinc and copper (Greenough et al., 2011) and APP in iron export (see ARF related news story on Duce et al., 2010). In the current paper, first author Peng Lei and colleagues focused on tau but ended up extending APP’s function in iron metabolism beyond Alzheimer’s and into Parkinson’s, noted Jack Rogers of Massachusetts General Hospital in Boston, who was not involved with this study but has collaborated with Bush in the past.
Although tau knockout mice have been around for a decade, they have no neurodegeneration (Dawson et al., 2001). However, scientists had not looked beyond seven months, Bush said. Lei and colleagues decided to wait until the animals reached a year old. “Lo and behold, 12 months onward their brains fall to pieces,” Bush said.
At one year, the brains of tau knockout mice weighed less than wild-type mouse brains of the same age, and their neocortex and cerebellar cortex were atrophied. They also had fewer dopaminergic neurons in the substantia nigra and performed poorly on locomotor tests. Most relevant to Lei and Bush’s interests, the mice accumulated iron in the cortex, hippocampus, and substantia nigra, and treatment with the Parkinson’s drug L-dopa reversed the motor symptoms.
The aged tau knockout mice represent an interesting new model for PD, commented Julie Andersen of the Buck Institute for Research on Aging in Novato, California, who was not involved with the paper. The model is a chronic, age-related condition, unlike the commonly used acute parkinsonism model caused by the chemical MPTP. On the con side, she added that the neurodegeneration seems to involve less dopaminergic neuron loss than human Parkinson’s, and it occurs not only in the substantia nigra, but also in the ventral tegmental area. “It is not perfect,” she said, “but then, no mouse model for neurodegeneration is.”
Could iron and tau be connected in people? Lei examined brain tissue from people who died with Parkinson’s and detected less soluble tau, but more iron, in their substantia nigras than in the same region from age-matched controls. Other scientists have observed lowered tau concentrations in the tauopathies Alzheimer’s and frontotemporal dementia (Ksiezak-Reding et al., 1988; Zhukareva et al., 2003).
The group has been extensively testing the metal-chelating drug clioquinol as a therapeutic. Bush and Andersen used it to protect against MPTP-induced symptoms in mice (see ARF related news story on Kaur et al., 2003), and Bush and colleagues used it to bust plaques in AD model mice (see ARF related news story on Cherny et al., 2001) and treat people with AD in a pilot study (see ARF related news story on Ritchie et al., 2003). Added to mouse chow, clioquinol blocked iron accumulation, neurodegeneration, and Parkinson’s-like symptoms seen in untreated tau-deficient mice as they aged. “It worked brilliantly,” Bush said.
The inverse relationship between iron and tau reminded the researchers of their discoveries with APP and iron. They used primary cortical neurons from the tau knockout strain to look for effects on APP. Although the tau-negative neurons contained plenty of APP, it failed to mature and reach the cell surface. The knockout neurons accumulated iron and were sensitive to iron toxicity. The findings suggest that tauopathies might not only be caused by a gain of toxic function due to neurofibrillary tangles, but also a loss of tau’s natural function in iron homeostasis, Andersen said. “APP, tau, etc., play a critical physiological role,” said George Perry of the University of Texas at San Antonio, who was not involved with the study. “Those processes are really part of how cells regulate themselves normally.”
The paper “adds to the evidence that iron accumulation, which continues into old age, may be part of the ‘age’ component of age-related neurodegenerative diseases such as AD, PD, and HD, and also why men (who have higher brain iron levels than women) may get these diseases earlier than women,” wrote George Bartzokis of the University of California, Los Angeles, in an e-mail to ARF (Bartzokis et al., 2007). Bartzokis was not involved in the study.
Returning iron levels to normal, Bush thinks, should be therapeutic. Prana Biotechnology Limited in Parkville, Australia, a company Bush co-founded but is no longer associated with, has tested a second-generation clioquinol-like compound called PBT2 in Alzheimer’s, and is starting a Huntington’s trial. In addition, Rogers warned that researchers developing therapies targeted at APP or tau might want to monitor effects on iron metabolism.—Amber Dance.
Reference:
Lei P, Ayton S, Finkelstein DI, Spoerri L, Ciccotosto GD, Wright DK, Wong BX, Adlard PA, Cherny RA, Lam LQ, Roberts BR, Volitakis I, Egan GF, McLean CA, Cappai R, Duce JA, Bush AI. Tau deficiency induces parkinsonism with dementia by impairing APP-mediated iron export. Nat Med. 2012 Jan 29. Doi:10.1038/nm.2613. Abstract
We are about 95% below our highest share price for the last 4.5 years. Where was that high?...1$!
"Good night and sweet dreams." I think you need to wake up to the bad and bitter reality...
Ps. Did you here about that polo club Founder and wealthy heir to a Texas AC empire who adopted his girlfriend? He wants to "trust" a portion of his wealth to her (thus, himself) so that the college kid he killed while he was drunk, coked up, and driving his Bentley, would not be able to access more of his money in a civil settlement. This guy deserves to live a very long and painful life:
1)http://www.sun-sentinel.com/news/palm-beach/fl-polo-club-owner-crash-20100428,0,6903204.story
2) http://www.sun-sentinel.com/news/palm-beach/fl-goodman-polo-case-20110126,0,4463384.story
3)http://www.sun-sentinel.com/news/palm-beach/wellington/pb-john-goodman-money-20111003,0,3679223.story
4)The final 'low' blow?: http://www.sun-sentinel.com/news/palm-beach/wellington/pb-john-goodman-adoption-latest-20120203,0,4232014.story
OT-Make that the 3rd: Remember the monthly debit card fees the large banks wanted to charge for their customers recently?:
http://www.washingtonpost.com/business/economy/bank-of-american-drops-debit-card-fee/2011/11/01/gIQADvugcM_story.html
Bank of America scraps debit card fee after consumer backlash
By Ylan Q. Mui, Published: November 1
They called it the fee that went too far.
For the past month, consumers have been railing against a new Bank of America charge requiring customers to pay $5 a month to use their debit cards for purchases. More than 300,000 people signed an online petition to stop the planned fee. More than 21,000 people pledged to close their Bank of America checking accounts. One cable news anchor cut up her card on the air.
?Empowered consumers are forcing some of America’s largest corporations, from Apple to Bank of America, to make radical changes to products or policies.
It was a classic David-and-Goliath fight, fueled by the growing populist outrage against the nation’s financial system. On Tuesday, the little guy won: Bank of America announced that it was abandoning the fee.
“This is one to go down in the history books, I think,” said Norma Garcia, manager of financial services at Consumers Union, an advocacy group. “It’s just a $5 fee, but it really is symbolic of so much more.”
Over the past year, consumers have wielded the power of social media to battle companies over issues large and small. When a Chicago jewelry artist accused Urban Outfitters on her blog of copying her designs, her post went viral and the company pulled the item within a day. Netflix subscribers persuaded the company to halt plans to spin off its DVD-rental business by bombarding it with more than 27,000 comments.
Bank of America was not the only — or even the first — to float the idea of charging customers to use their debit cards. But its plan became public a month ago, just as the Occupy Wall Street protests began to gain national momentum. Though Occupy supporters are motivated by a wide range of social ills, including climate change and income inequality, there seemed to be consensus that Bank of America’s fee was a prime example of the banking industry run amuck.
Take the online petition started by 22-year-old D.C. resident Molly Katchpole on Change.org calling on the bank to drop the fee. Though not affiliated with the Occupy protests, the letter tapped into the same vein of populist anger, recounting the bank’s role in the financial crisis and calling the fee “despicable.”
On Oct. 1, 100 people signed Katchpole’s petition. The next day, the number shot to 3,000. The day after, it was 75,000. By Tuesday, more than 300,000 people had joined, making it the largest consumer campaign ever on the site.
“The success off this campaign proves that ordinary people can successfully stand up to even the largest corporations,” Katchpole said in a statement.
Bank of America was quick to point to new federal regulations as the catalyst for the fee, saying that the “economics of offering a debit card have changed.”
Banks are now prohibited from charging most overdraft fees, eliminating a previously lucrative practice. And last month, rules went into effect that limit the amount of money banks can receive from retailers when consumers swipe their debit cards. The regulations are expected to cost banks billions of dollars.
But Washington fired back. President Obama called the fee “not good business practice.” Democratic Rep. Brad Miller of North Carolina, where Bank of America is based, introduced a bill to make it easier for consumers to switch checking accounts. Rep. Peter Welch (D-Vt.) met last week with the Justice Department after calling for an investigation into the debit card fee.
“They overreached,” Welch said. “It was customer reaction, there was competitor reaction and there was congressional reaction.”
Credit unions and community banks have reported a surge of interest — and new accounts — as consumers seek alternatives. Roughly 51,000 people have signed up to move their money out of large banks on Saturday, according to the Progressive Change Campaign Committee, which is helping to organize the event. The group said that more than 21,000 are Bank of America customers.
“This is a victory for consumers who are voting with their feet,” said Ed Mierzwinski, head of the consumer program at U.S. PIRG. “For the first time, a bank fee has bitten the bank.”
For other banks charging a debit card fee or testing one, the response has been resounding: Abandon ship. Wells Fargo, Chase, Regions and SunTrust all canceled fees last week, which left Bank of America the last bank standing.
“We have listened to our customers very closely over the last few weeks and recognize their concern with our proposed debit usage fee,” David Darnell, co-chief operating officer at Bank of America, said Tuesday in a statement. “Our customers’ voices are most important to us. As a result, we are not currently charging the fee and will not be moving forward with any additional plans to do so.”
The move came too late for Matt Hrono, 21, of Boston. He stopped using his Bank of America checking account after learning about the planned charge and won’t go back despite the bank’s about-face.
“Just the fact that they even considered it, that just shows how ridiculous they are and how utterly greedy they are,” he said.
Instead, Hrono switched to USAA, which has touted its stance against a debit card fee. When a customer service representative asked why he was joining the bank, he mentioned the charge at Bank of America. It was a refrain she had heard before.
“You’re not the first person today who said the same thing,” Hrono said she told him.
And more impressively, the Nasdaq index reached levels last seen in December 2000.
Does Brain Hypoxia Help Kick Off Alzheimer’s Pathology?
http://www.alzforum.org/new/detail.asp?id=3002
16 December 2011. Why some seniors develop sporadic Alzheimer’s disease and others do not is still largely a mystery. Now, two new human studies implicate loss of oxygen in the brain as a possible culprit that touches off early AD pathology. In the December 14 PLoS One, researchers led by Henrik Zetterberg at the University of Gothenburg, Mölndal, Sweden, report that cardiac arrest, an extreme form of hypoxia, causes a massive surge in blood Aß levels. Furthermore, the size and duration of the Aß spike correlates with worse clinical outcomes, suggesting that more severe hypoxia results in greater Aß release. Meanwhile, researchers led by Matej Oresic at the VTT Technical Research Centre of Finland, Espoo, analyzed panels of metabolites in the blood of people with mild cognitive impairment (MCI) or AD. In a Translational Psychiatry paper published online December 13, they report that a marker of hypoxia distinguishes people with MCI who go on to develop AD from those who remain stable. Together, these studies suggest that hypoxia is a factor that tilts an aging brain toward AD.
The hypothesis might help explain the consistent link seen between cardiovascular health and AD risk (see, e.g., homocysteine and hypertension; Solomon et al., 2009; Li et al., 2011), and even the association of age with AD. “Oxygen levels in the brain can drop with aging as cerebral blood flow decreases, which could be driving production of Aß,” noted Kim Green at the University of California, Irvine.
Green was not involved in either study, but has seen similar effects in 3xTgAD mice. In these animals, temporarily decreasing blood flow to the brain jacked up expression of ß-secretase (BACE), one of two enzymes that produce Aß, and kept Aß levels high for several weeks (see Koike et al., 2010). Low atmospheric oxygen also pushes mice into the disease state through this BACE-mediated mechanism (see ARF related news story on Sun et al., 2006). Similarly, other studies reported that reducing blood flow increases brain Aß in rodents (see Wang et al., 2010). Brain Aß is also up in humans who died after strokes or heart attacks (see Qi et al., 2007 and Wisniewski and Maslinska, 1996). And a recent large prospective epidemiological study showed that elderly women with sleep apnea have an almost doubled risk of developing cognitive impairment within five years compared to those who sleep normally, again implicating hypoxia in early neurodegeneration (see ARF related news story on Yaffe et al., 2011).
Zetterberg and colleagues wanted to look at the relationship between hypoxia and Aß levels in living humans. To do this, they measured Aß levels in blood serum using an ultrasensitive technology called Single Molecule Arrays, developed by coauthor David Wilson and colleagues at Quanterix Corporation, Cambridge, Massachusetts (see Rissin et al., 2010 and Rissin et al., 2011). The scientists captured serum Aß with antibodies fixed to beads, then analyzed the samples in tiny, femtoliter-sized wells that held one bead apiece. They quantified Aß levels by measuring the intensity of a fluorescent reaction produced by a reporter enzyme. Because the signal is concentrated in a minute volume, this method can measure serum concentrations as low as 0.04 pg/mL, making it far more sensitive than conventional enzyme-linked immunosorbent assay (ELISA) methods, the authors report.
The researchers took blood samples from 25 patients who were resuscitated after cardiac arrest, collecting blood at regular intervals from one hour to about four days after their heart attack. The patients’ average age was over 60, but ranged as low as 25. Regardless of age, all patients showed a massive increase in blood Aß levels over the course of sampling. The hike averaged around sevenfold, but went as high as 70-fold. This is a far greater upsurge in Aß levels than seen in other conditions, such as in familial AD, Zetterberg noted. The magnitude and duration of the Aß surge correlated with patient outcome, meaning the spikes were shorter and smaller in patients who recovered good cognitive function, while the brains of patients who died or remained in a vegetative state continued to pump out massive and rising levels of the peptide. Notably, the researchers saw no relationship between clinical outcome and initial levels of Aß taken after cardiac arrest, nor any interaction with ApoE genotype or gender.
The data add to the evidence that hypoxia may be a causative factor in sporadic AD, Zetterberg told ARF. He suggested that future studies might examine serum Aß levels in other conditions associated with hypoxia, such as sleep apnea, as well as look more closely at brain vasculature in AD patients. The Aß upswell in blood probably reflects increased production of the peptide in brain, but it is also possible that the surge is due simply to greater leakage from the brain, perhaps through breakdown of the blood-brain barrier, the authors note. For his part, Green speculated that after hypoxia, Aß production may ramp up throughout the body, not just in the brain.
The second study, by Oresic and colleagues, also ties markers in human blood to hypoxia in the brain. While other groups have identified protein panels in blood that help predict progression to AD (see ARF related news story on Ray et al., 2007; O’Bryant et al., 2010), Oresic and colleagues focused instead on lipids and other small metabolites. They analyzed fasting blood samples from more than 140 people with MCI, nearly 40 people with AD, and almost 50 healthy controls. The researchers followed up with the people who had MCI roughly 2.5 years later to see who had developed AD and who had remained stable.
In agreement with previous research, the authors found that people with AD tend to have lower levels of many lipids, including sterols, phosphatidylcholines, and sphingolipids, compared to controls (see, e.g., Han et al., 2001; Puglielli et al., 2003; He et al., 2010; Han et al., 2011). Intriguingly, however, Oresic and colleagues saw this altered lipid profile in only a minority of the people with MCI who progressed to AD. In other words, lipid profile did not predict who would develop Alzheimer’s.
Instead, they identified three metabolites in blood that together distinguished between progressors and non-progressors in the MCI group with a sensitivity and specificity of about 80 and 70 percent, respectively. The most predictive of the three was an organic acid, 2,4-dihydroxybutanoic acid, which is more abundant in cerebrospinal fluid (CSF) than in blood by two orders of magnitude. Its levels were higher in people whose disease progressed. Little is known about its biochemistry, Oresic said, except that it is overproduced in low oxygen conditions and generally considered a marker of hypoxia. Further supporting a link between disease progression and hypoxia, the researchers found that the pentose phosphate pathway, which metabolizes glucose to lactate under hypoxic conditions (see Hakim et al., 1976), was more active in MCI progressors compared to non-progressors.
“There is a biochemical signature, a specific set of metabolites, that seems to predict the onset of the disease years in advance,” Oresic told ARF. In the next year, he is planning to do pilot studies in the clinic to see if these blood markers could serve as a simple, inexpensive way to flag people with early cognitive problems who are most at risk for progressing to AD. He will also try to replicate these findings in a larger cohort, as well as look at metabolite profiles in CSF and biopsy samples.—Madolyn Bowman Rogers.
References:
Zetterberg H, Mörtberg E, Song L, Chang L, Provuncher GK, Patel PP, Ferrell E, Fournier DR, Kan CW, Campbell TG, Meyer R, Rivnak AJ, Pink BA, Minnehan KA, Piech T, Rissin DM, Duffy DC, Rubertsson S, Wilson DH, Blennow K. Hypoxia due to cardiac arrest induces a time-dependent increase in serum amyloid ß levels in humans. PLoS One. 2011. Abstract
Oresic M, Hyötyläinen T, Herukka SK, Sysi-Aho M, Mattila I, Seppänan-Laakso T, Julkunen V, Gopalacharyulu PV, Hallikainen M, Koikkalainen J, Kivipelto M, Helisalmi S, Lötjönen J, Soininen H. Metabolome in progression to Alzheimer’s disease. Transl Psychiatr. 2011.
Americans' Political Views Not So Far Apart
By Stephanie Pappas | LiveScience.com – 20 hrs ago
http://news.yahoo.com/americans-political-views-not-far-apart-155803567.html
SAN DIEGO — In an election year, it's hard to turn on the television or read a newspaper without getting the sense that Americans are becoming ever more divided into red versus blue. But a new study finds that perception may be downright wrong.
In fact, political polarization among the public has barely budged at all over the past 40 years, according to research presented here on Jan. 27 at the annual meeting of the Society for Personality and Social Psychology. But, crucially, people vastly overestimate how polarized the American public is — a tendency toward exaggeration that is especially strong in the most extreme Democrats and Republicans. (The results do not apply to Congress, politicians or media pundits, but rather to the general public.)
"Strongly identified Republicans or Democrats perceive and exaggerate polarization more than weakly identified Republicans or Democrats or political independents," said study researcher John Chambers, a professor of psychology at the University of Florida.
The people who see the world split into two opposing factions are also most likely to vote and become politically active, Chambers said in a talk at the meeting. This means that while real growing polarization is illusory, the perception of polarization could drive the political process.
Growing divide?
Inspired by polling data showing that two-thirds of Americans believe the United States is becoming more politically polarized, with the gap between the political parties widening, Chambers and his colleagues looked at nationally representative data stretching from 1970 to 2004. More than 43,000 respondents over the years have participated in the large-scale American National Election Survey, though not all answered all questions. So the researchers had between 4,000 and 26,000 individuals to work with on various questions.
The respondents indicated their political beliefs by answering questions on their opinions on a wild variety of issues, from government-provided health care to defense spending to women's equality. They also reported how they believe a "typical" Republican and Democrat would feel about these same issues.
"Using these two measures, we were able to look at actual and perceived differences in polarization," Chambers said.
They found that actual polarization has remained steady since the 1970s. The historical responses also showed that people have always overestimated polarization. Even decades ago, in times now remembered as cooperative and cordial, people pegged political disagreements as much more vast than they really were. [Life's Extremes: Democrat vs. Republican]
When the researchers broke down the respondents by political positions, they found that not everyone judges polarization in the same way. Everyone overestimates it, but political independents are much closer to the mark than strong Republicans or strong Democrats, who tend to see the gulf between themselves and the other party as impossibly wide. Moderate Republicans and moderate Democrats were in-between, perceiving more polarization than independents but less than the extreme ends of the parties.
Projecting polarization
In a separate study also presented here, University of Colorado, Boulder, psychology professor Leaf Van Boven looked at why people at the political extremes might overestimate polarization. The answer seems to be that they project their own strong, emotional thought processes onto others, Van Boven and his colleagues concluded. In their study, they presented students with a fictional policy that would try to lure out-of-state students to campus with preferential treatment, including first pick of classes and dorms.
Unsurprisingly, this fake proposal yielded polarized views. "This proposal is bulls---!" one student wrote. Another indicated support, adding, "I am biased, because I am out of state, and I want the sweet hookups."
When the researchers asked students to indicate how they though other students felt about the proposal, those who themselves opposed or supported it most strongly assumed that others would also feel strongly, in support or opposition.
When asked how they came to their conclusions about the proposal and how they believed others came to their conclusions, the students gave themselves credit for more fairness and less self-interest than they did others. But they also assumed that everyone gave equal weight to emotion and extensive thought.
"If someone has a strong moral reaction and says 'This is a moral issue', they may reasonably think that others, both on their side and other side, will think in the same way," Van Boven explained.
While political elites, such as political operatives, Congress and media pundits, are "another story," according to Chambers, the results of the polarization studies provide "reason for optimism and hope," he said.
"Although we tend to see the world as divided between blue and red, in reality, the world has much greater shades of purple," Chambers said. "There is more common ground than we realize."
Andrew Sullivan: How Obama's Long Game Will Outsmart His Critics
Jan 16, 2012 12:00 AM EST
http://www.thedailybeast.com/newsweek/2012/01/15/andrew-sullivan-how-obama-s-long-game-will-outsmart-his-critics.html
The right calls him a socialist, the left says he sucks up to Wall Street, and independents think he's a wimp. Andrew Sullivan on how the president may just end up outsmarting them all.
You hear it everywhere. Democrats are disappointed in the president. Independents have soured even more. Republicans have worked themselves up into an apocalyptic fervor {(lol)}. And, yes, this is not exactly unusual.
A president in the last year of his first term will always get attacked mercilessly by his partisan opponents, and also, often, by the feistier members of his base. And when unemployment is at remarkably high levels, and with the national debt setting records, the criticism will—and should be—even fiercer. But this time, with this president, something different has happened. It’s not that I don’t understand the critiques of Barack Obama from the enraged right and the demoralized left. It’s that I don’t even recognize their description of Obama’s first term in any way. The attacks from both the right and the left on the man and his policies aren’t out of bounds. They’re simply—empirically—wrong.
A caveat: I write this as an unabashed supporter of Obama from early 2007 on. I did so not as a liberal, but as a conservative-minded independent appalled by the Bush administration’s record of war, debt, spending, and torture. I did not expect, or want, a messiah. I have one already, thank you very much. And there have been many times when I have disagreed with decisions Obama has made—to drop the Bowles-Simpson debt commission, to ignore the war crimes of the recent past, and to launch a war in Libya without Congress’s sanction, to cite three. But given the enormity of what he inherited, and given what he explicitly promised, it remains simply a fact that Obama has delivered in a way that the unhinged right and purist left have yet to understand or absorb. Their short-term outbursts have missed Obama’s long game—and why his reelection remains, in my view, as essential for this country’s future as his original election in 2008.
The right’s core case is that Obama has governed as a radical leftist attempting a “fundamental transformation” of the American way of life. Mitt Romney accuses the president of making the recession worse, of wanting to turn America into a European welfare state, of not believing in opportunity or free enterprise, of having no understanding of the real economy, and of apologizing for America and appeasing our enemies. According to Romney, Obama is a mortal threat to “the soul” of America and an empty suit who couldn’t run a business, let alone a country.
Leave aside the internal incoherence—how could such an incompetent be a threat to anyone? None of this is even faintly connected to reality—and the record proves it. On the economy, the facts are these. When Obama took office, the United States was losing around 750,000 jobs a month. The last quarter of 2008 saw an annualized drop in growth approaching 9 percent. This was the most serious downturn since the 1930s, there was a real chance of a systemic collapse of the entire global financial system, and unemployment and debt—lagging indicators—were about to soar even further. No fair person can blame Obama for the wreckage of the next 12 months, as the financial crisis cut a swath through employment. Economies take time to shift course.
But Obama did several things at once: he continued the bank bailout begun by George W. Bush, he initiated a bailout of the auto industry, and he worked to pass a huge stimulus package of $787 billion.
All these decisions deserve scrutiny. And in retrospect, they were far more successful than anyone has yet fully given Obama the credit for. The job collapse bottomed out at the beginning of 2010, as the stimulus took effect. Since then, the U.S. has added 2.4 million jobs. That’s not enough, but it’s far better than what Romney would have you believe, and more than the net jobs created under the entire Bush administration. In 2011 alone, 1.9 million private-sector jobs were created, while a net 280,000 government jobs were lost. Overall government employment has declined 2.6 percent over the past 3 years. (That compares with a drop of 2.2 percent during the early years of the Reagan administration.) To listen to current Republican rhetoric about Obama’s big-government socialist ways, you would imagine that the reverse was true. It isn’t.
The right claims the stimulus failed because it didn’t bring unemployment down to 8 percent in its first year, as predicted by Obama’s transition economic team. Instead, it peaked at 10.2 percent. But the 8 percent prediction was made before Obama took office and was wrong solely because it relied on statistics that guessed the economy was only shrinking by around 4 percent, not 9. Remove that statistical miscalculation (made by government and private-sector economists alike) and the stimulus did exactly what it was supposed to do. It put a bottom under the free fall. It is not an exaggeration to say it prevented a spiral downward that could have led to the Second Great Depression.
You’d think, listening to the Republican debates, that Obama has raised taxes. Again, this is not true. Not only did he agree not to sunset the Bush tax cuts for his entire first term, he has aggressively lowered taxes on most Americans. A third of the stimulus was tax cuts, affecting 95 percent of taxpayers; he has cut the payroll tax, and recently had to fight to keep it cut against Republican opposition. His spending record is also far better than his predecessor’s. Under Bush, new policies on taxes and spending cost the taxpayer a total of $5.07 trillion. Under Obama’s budgets both past and projected, he will have added $1.4 trillion in two terms. Under Bush and the GOP, nondefense discretionary spending grew by twice as much as under Obama. Again: imagine Bush had been a Democrat and Obama a Republican. You could easily make the case that Obama has been far more fiscally conservative than his predecessor—except, of course, that Obama has had to govern under the worst recession since the 1930s, and Bush, after the 2001 downturn, governed in a period of moderate growth. It takes work to increase the debt in times of growth, as Bush did. It takes much more work to constrain the debt in the deep recession Bush bequeathed Obama.
The great conservative bugaboo, Obamacare, is also far more moderate than its critics have claimed. The Congressional Budget Office has projected it will reduce the deficit, not increase it dramatically, as Bush’s unfunded Medicare Prescription Drug benefit did. It is based on the individual mandate, an idea pioneered by the archconservative Heritage Foundation, Newt Gingrich, and, of course, Mitt Romney, in the past. It does not have a public option; it gives a huge new client base to the drug and insurance companies; its health-insurance exchanges were also pioneered by the right. It’s to the right of the Clintons’ monstrosity in 1993, and remarkably similar to Nixon’s 1974 proposal. Its passage did not preempt recovery efforts; it followed them. It needs improvement in many ways, but the administration is open to further reform and has agreed to allow states to experiment in different ways to achieve the same result. It is not, as Romney insists, a one-model, top-down prescription. Like Obama’s Race to the Top education initiative, it sets standards, grants incentives, and then allows individual states to experiment. Embedded in it are also a slew of cost-reduction pilot schemes to slow health-care spending. Yes, it crosses the Rubicon of universal access to private health care. But since federal law mandates that hospitals accept all emergency-room cases requiring treatment anyway, we already obey that socialist principle—but in the most inefficient way possible. Making 44 million current free-riders pay into the system is not fiscally reckless; it is fiscally prudent. It is, dare I say it, conservative.
On foreign policy, the right-wing critiques have been the most unhinged. Romney accuses the president of apologizing for America, and others all but accuse him of treason and appeasement. Instead, Obama reversed Bush’s policy of ignoring Osama bin Laden, immediately setting a course that eventually led to his capture and death. And when the moment for decision came, the president overruled both his secretary of state and vice president in ordering the riskiest—but most ambitious—plan on the table. He even personally ordered the extra helicopters that saved the mission. It was a triumph, not only in killing America’s primary global enemy, but in getting a massive trove of intelligence to undermine al Qaeda even further. If George Bush had taken out bin Laden, wiped out al Qaeda’s leadership, and gathered a treasure trove of real intelligence by a daring raid, he’d be on Mount Rushmore by now. But where Bush talked tough and acted counterproductively, Obama has simply, quietly, relentlessly decimated our real enemies, while winning the broader propaganda war. Since he took office, al Qaeda’s popularity in the Muslim world has plummeted.
Obama’s foreign policy, like Dwight Eisenhower’s or George H.W. Bush’s, eschews short-term political hits for long-term strategic advantage. It is forged by someone interested in advancing American interests—not asserting an ideology and enforcing it regardless of the consequences by force of arms. By hanging back a little, by “leading from behind” in Libya and elsewhere, Obama has made other countries actively seek America’s help and reappreciate our role. As an antidote to the bad feelings of the Iraq War, it has worked close to perfectly.
But the right isn’t alone in getting Obama wrong. While the left is less unhinged in its critique, it is just as likely to miss the screen for the pixels. From the start, liberals projected onto Obama absurd notions of what a president can actually do in a polarized country, where anything requires 60 Senate votes even to stand a chance of making it into law. They have described him as a hapless tool of Wall Street, a continuation of Bush in civil liberties, a cloistered elitist unable to grasp the populist moment that is his historic opportunity. They rail against his attempts to reach a Grand Bargain on entitlement reform. They decry his too-small stimulus, his too-weak financial reform, and his too-cautious approach to gay civil rights. They despair that he reacts to rabid Republican assaults with lofty appeals to unity and compromise.
They miss, it seems to me, two vital things. The first is the simple scale of what has been accomplished on issues liberals say they care about. A depression was averted. The bail-out of the auto industry was—amazingly—successful. Even the bank bailouts have been repaid to a great extent by a recovering banking sector. The Iraq War—the issue that made Obama the nominee—has been ended on time and, vitally, with no troops left behind. Defense is being cut steadily, even as Obama has moved his own party away from a Pelosi-style reflexive defense of all federal entitlements. Under Obama, support for marriage equality and marijuana legalization has crested to record levels. Under Obama, a crucial state, New York, made marriage equality for gays an irreversible fact of American life. Gays now openly serve in the military, and the Defense of Marriage Act is dying in the courts, undefended by the Obama Justice Department. Vast government money has been poured into noncarbon energy investments, via the stimulus. Fuel-emission standards have been drastically increased. Torture was ended. Two moderately liberal women replaced men on the Supreme Court. Oh, yes, and the liberal holy grail that eluded Johnson and Carter and Clinton, nearly universal health care, has been set into law. Politifact recently noted that of 508 specific promises, a third had been fulfilled and only two have not had some action taken on them. To have done all this while simultaneously battling an economic hurricane makes Obama about as honest a follow-through artist as anyone can expect from a politician.
What liberals have never understood about Obama is that he practices a show-don’t-tell, long-game form of domestic politics. What matters to him is what he can get done, not what he can immediately take credit for. And so I railed against him for the better part of two years for dragging his feet on gay issues. But what he was doing was getting his Republican defense secretary and the chairman of the Joint Chiefs to move before he did. The man who made the case for repeal of “don’t ask, don’t tell” was, in the end, Adm. Mike Mullen. This took time—as did his painstaking change in the rule barring HIV-positive immigrants and tourists—but the slow and deliberate and unprovocative manner in which it was accomplished made the changes more durable. Not for the first time, I realized that to understand Obama, you have to take the long view. Because he does.
Or take the issue of the banks. Liberals have derided him as a captive of Wall Street, of being railroaded by Larry Summers and Tim Geithner into a too-passive response to the recklessness of the major U.S. banks. But it’s worth recalling that at the start of 2009, any responsible president’s priority would have been stabilization of the financial system, not the exacting of revenge. Obama was not elected, despite liberal fantasies, to be a left-wing crusader. He was elected as a pragmatic, unifying reformist who would be more responsible than Bush.
And what have we seen? A recurring pattern. To use the terms Obama first employed in his inaugural address: the president begins by extending a hand to his opponents; when they respond by raising a fist, he demonstrates that they are the source of the problem; then, finally, he moves to his preferred position of moderate liberalism and fights for it without being effectively tarred as an ideologue or a divider. This kind of strategy takes time. And it means there are long stretches when Obama seems incapable of defending himself, or willing to let others to define him, or simply weak. I remember those stretches during the campaign against Hillary Clinton. I also remember whose strategy won out in the end.
This is where the left is truly deluded. By misunderstanding Obama’s strategy and temperament and persistence, by grandstanding on one issue after another, by projecting unrealistic fantasies onto a candidate who never pledged a liberal revolution, they have failed to notice that from the very beginning, Obama was playing a long game. He did this with his own party over health-care reform. He has done it with the Republicans over the debt. He has done it with the Israeli government over stopping the settlements on the West Bank—and with the Iranian regime, by not playing into their hands during the Green Revolution, even as they gunned innocents down in the streets. Nothing in his first term—including the complicated multiyear rollout of universal health care—can be understood if you do not realize that Obama was always planning for eight years, not four. And if he is reelected, he will have won a battle more important than 2008: for it will be a mandate for an eight-year shift away from the excesses of inequality, overreach abroad, and reckless deficit spending of the last three decades. It will recapitalize him to entrench what he has done already and make it irreversible.
Yes, Obama has waged a war based on a reading of executive power that many civil libertarians, including myself, oppose. And he has signed into law the indefinite detention of U.S. citizens without trial (even as he pledged never to invoke this tyrannical power himself). But he has done the most important thing of all: excising the cancer of torture from military detention and military justice. If he is not reelected, that cancer may well return. Indeed, many on the right appear eager for it to return.
Sure, Obama cannot regain the extraordinary promise of 2008. We’ve already elected the nation’s first black president and replaced a tongue-tied dauphin with a man of peerless eloquence. And he has certainly failed to end Washington’s brutal ideological polarization, as he pledged to do. But most Americans in polls rightly see him as less culpable for this impasse than the GOP. Obama has steadfastly refrained from waging the culture war, while the right has accused him of a “war against religion.” He has offered to cut entitlements (and has already cut Medicare), while the Republicans have refused to raise a single dollar of net revenue from anyone. Even the most austerity-driven government in Europe, the British Tories, are to the left of that. And it is this Republican intransigence—from the 2009 declaration by Rush Limbaugh that he wants Obama “to fail” to the Senate Majority Leader Mitch McConnell’s admission that his primary objective is denying Obama a second term—that has been truly responsible for the deadlock. And the only way out of that deadlock is an electoral rout of the GOP, since the language of victory and defeat seems to be the only thing it understands.
If I sound biased, that’s because I am. Biased toward the actual record, not the spin; biased toward a president who has conducted himself with grace and calm under incredible pressure, who has had to manage crises not seen since the Second World War and the Depression, and who as yet has not had a single significant scandal to his name. “To see what is in front of one’s nose needs a constant struggle,” George Orwell once wrote. What I see in front of my nose is a president whose character, record, and promise remain as grotesquely underappreciated now as they were absurdly hyped in 2008. And I feel confident that sooner rather than later, the American people will come to see his first term from the same calm, sane perspective. And decide to finish what they started.
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Andrew Sullivan, former editor of The New Republic, weekly columnist for the Sunday Times of London, brought his hugely popular blog, The Dish, to the Daily Beast in 2011. He's the author of several books, including "Virtually Normal," "Love Undetectable," and "The Conservative Soul."
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My father-in-law used to share that quote with my wife and I (rest his soul). As with many such sayings, there is always some truth to it. Thanks for the reiteration. I often thought about his words, but never remembered how it went, or even with whom they originated.
I suggest you spend your time and money more wisely if you feel the end is near. Why waste it on any more virtual interacting and pointless investing, respectively? Travel, give, live, love...indulge. The uncertainty has been taken out of the equation.
Ps. Do you believe everything you read?