Mind: A Compromise on Defining and Diagnosing Mental Disorders

They plotted a revolution, fell to debating among themselves, and in the end overturned very little except their own expectations.

But the effort itself was a valuable guide for anyone who has received a psychiatric diagnosis, or anyone who might get one.

This month, the American Psychiatric Association announced that its board of trustees had approved the fifth edition of the association’s influential diagnostic manual — the so-called bible of mental disorders — ending more than five years of sometimes acrimonious, and often very public, controversy.

The committee of doctors appointed by the psychiatric association had attempted to execute a paradigm shift, changing how mental disorders are conceived and posting its proposals online for the public to comment. And comment it did: Patient advocacy groups sounded off, objecting to proposed changes in the definitions of depression and Asperger syndrome, among other diagnoses. Outside academic researchers did, too. A few committee members quit in protest.

The final text, which won’t be fully available until publication this spring, has already gotten predictably mixed reviews. “Given the challenges in a field where objective lines are hard to draw, they did a solid job,” said Dr. Michael First, a psychiatrist at Columbia who edited a previous version of the manual and was a consultant on this one.

Others disagreed. “This is the saddest moment in my 45-year career of practicing, studying and teaching psychiatry,” wrote Dr. Allen Frances, the chairman of a previous committee who has been one of the most vocal critics, in a blog post about the new manual, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM5.

Yet many experts inside and outside the process said the final document was not radically different from the previous version, and its lessons more mundane than the rhetoric implied. The status quo is hard to budge, for one. And when changes do happen, they are not necessarily the ones that were intended.

The new manual does extend the reach of psychiatry in some areas, as many critics feared it might. Hoarding is now a mental disorder (previously it was considered a symptom of obsessive-compulsive behavior). “Premenstrual dysphoric disorder,” a severe form of premenstrual syndrome, is also new (it was previously in the appendix).

And binge-eating disorder (also formerly in the appendix), a kind of severe, highly distressing gluttony, is now a full-blown diagnosis. This one by itself could tag millions of people considered healthy, if often overindulgent, with a psychiatric label, some experts said.

But the deeper story is one of compromise. It is most evident in how the committee handled three of the thorniest diagnoses in psychiatry: autism, depression and pediatric bipolar disorder.

The group working on depression declared early on that it wanted to eliminate the so-called bereavement exclusion, which stated that grieving the loss of a loved one should not be considered a clinical disorder, though it shares many of the same outward signs. Grief has always been a normal reaction to death, not a kind of depression.

Advocacy and support groups, such as those representing people who have lost a child, objected furiously to the idea that the bereaved might be given a diagnosis of depression.

“This was just astonishing, that they would eliminate the exclusion, and a distortion of the research on the subject,” said Jerome Wakefield, a professor of social work and psychiatry at New York University, who did not work on the manual.

In the end the committee cut a deal. It eliminated the grief exclusion but added a note in the text, reminding doctors that any significant loss — of a job, a relationship, a home — could cause depressive symptoms and should be carefully investigated.

“It’s like they took it all back,” Dr. Wakefield said. “I don’t like the way it was done — in a footnote — but it’s there.”

The debate over autism was even more furious, and it resulted in a similar rapprochement.

From the outset, the committee intended to tighten the definition of autism and simplify it, eliminating related labels like Asperger syndrome and “pervasive developmental disorder not otherwise specified,” or PDD-NOS. The rate of diagnosis of such conditions has exploded over the past decade, in part due to the vagueness of the definitions, and the committee wanted to draw clearer boundaries.

It proposed a single “autism spectrum disorder” category, with stricter requirements.

Some outside researchers raised concerns. In January one of them, Dr. Fred Volkmar of the Yale School of Medicine, who had quit the committee in protest, presented research suggesting that 45 percent or more of people who currently had an autism or related diagnosis would not have one under the proposed revision.

Autism groups reacted immediately, fearing that the change in the diagnosis would deny services to children and families who need them.

The committee countered with its own study, suggesting that the new definition would exclude about 10 percent of people currently with a diagnosis. And again, the experts took a half step back.

The new, streamlined definition was approved, but with language that took into account a person’s diagnostic history. “It’s explicit that anyone who’s had an Asperger’s or autism or PDD-NOS diagnosis before is now included,” said Catherine Lord, a committee member who worked on the new definition and who is director of the Center for Autism and the Developing Brain in New York. “Essentially everyone gets in.”

Pediatric bipolar disorder posed a different challenge.

In the 1990s and 2000s, psychiatrists began giving aggressive, explosive children a diagnosis of bipolar disorder in increasing numbers. The trend appalled many patient advocates and doctors.

Bipolar disorder, which is characterized by episodes of depression and mania, had previously been an adult problem; now the diagnosis is given to children as young as 2 — along with powerful psychiatric drugs and tranquilizers that also cause rapid weight gain. The committee wanted to stop the trend in its tracks, said experts who were involved.

Most of the children treated for bipolar disorder did not have it, recent research found. The committee settled on an alternative label: “disruptive mood dysregulation disorder,” or D.M.D.D., which describes extreme hostility and outbursts beyond normal tantrums.

“They essentially wanted to have some place for these kids, and D.M.D.D. was all they had in their kit,” said Dr. Gabrielle Carlson, a child psychiatrist at Stony Brook University Medical Center, who provided some outside consultation. “These are mostly kids who have A.D.H.D. or what we would call oppositional defiant disorder, but with this explosive feature. They need help; you can’t wait forever. The question was what to call it, without pretending we know enough to saddle them with a lifelong diagnosis” like bipolar disorder.

D.M.D.D. has its own problems, as many experts were quick to point out. It could be a symptom of an underlying condition, as Dr. Carlson argues. It could “medicalize” frequent temper tantrums. It’s brand new, and no one knows how it will play out in practice.

But it is now in the book — because it was the best solution available, experts inside and outside of the revision process said.

From beginning to end, many experts said, the process of defining psychiatric diagnoses is very much like finding the right one for an individual: it’s a process of negotiation, in many cases.

“That’s one of the take-aways from all this, and I think it’s a good one,” Dr. Carlson said. “A diagnosis is a hypothesis. It’s a start, and you have to start somewhere. But that’s all it is.”

One of the committee’s most ambitious proposals was perhaps the least noticed: a commitment to update the book continually, when there’s good reason to, rather than once every decade or so in a giant heave. That was approved without much fanfare.

Read More..

Mind: A Compromise on Defining and Diagnosing Mental Disorders

They plotted a revolution, fell to debating among themselves, and in the end overturned very little except their own expectations.

But the effort itself was a valuable guide for anyone who has received a psychiatric diagnosis, or anyone who might get one.

This month, the American Psychiatric Association announced that its board of trustees had approved the fifth edition of the association’s influential diagnostic manual — the so-called bible of mental disorders — ending more than five years of sometimes acrimonious, and often very public, controversy.

The committee of doctors appointed by the psychiatric association had attempted to execute a paradigm shift, changing how mental disorders are conceived and posting its proposals online for the public to comment. And comment it did: Patient advocacy groups sounded off, objecting to proposed changes in the definitions of depression and Asperger syndrome, among other diagnoses. Outside academic researchers did, too. A few committee members quit in protest.

The final text, which won’t be fully available until publication this spring, has already gotten predictably mixed reviews. “Given the challenges in a field where objective lines are hard to draw, they did a solid job,” said Dr. Michael First, a psychiatrist at Columbia who edited a previous version of the manual and was a consultant on this one.

Others disagreed. “This is the saddest moment in my 45-year career of practicing, studying and teaching psychiatry,” wrote Dr. Allen Frances, the chairman of a previous committee who has been one of the most vocal critics, in a blog post about the new manual, the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM5.

Yet many experts inside and outside the process said the final document was not radically different from the previous version, and its lessons more mundane than the rhetoric implied. The status quo is hard to budge, for one. And when changes do happen, they are not necessarily the ones that were intended.

The new manual does extend the reach of psychiatry in some areas, as many critics feared it might. Hoarding is now a mental disorder (previously it was considered a symptom of obsessive-compulsive behavior). “Premenstrual dysphoric disorder,” a severe form of premenstrual syndrome, is also new (it was previously in the appendix).

And binge-eating disorder (also formerly in the appendix), a kind of severe, highly distressing gluttony, is now a full-blown diagnosis. This one by itself could tag millions of people considered healthy, if often overindulgent, with a psychiatric label, some experts said.

But the deeper story is one of compromise. It is most evident in how the committee handled three of the thorniest diagnoses in psychiatry: autism, depression and pediatric bipolar disorder.

The group working on depression declared early on that it wanted to eliminate the so-called bereavement exclusion, which stated that grieving the loss of a loved one should not be considered a clinical disorder, though it shares many of the same outward signs. Grief has always been a normal reaction to death, not a kind of depression.

Advocacy and support groups, such as those representing people who have lost a child, objected furiously to the idea that the bereaved might be given a diagnosis of depression.

“This was just astonishing, that they would eliminate the exclusion, and a distortion of the research on the subject,” said Jerome Wakefield, a professor of social work and psychiatry at New York University, who did not work on the manual.

In the end the committee cut a deal. It eliminated the grief exclusion but added a note in the text, reminding doctors that any significant loss — of a job, a relationship, a home — could cause depressive symptoms and should be carefully investigated.

“It’s like they took it all back,” Dr. Wakefield said. “I don’t like the way it was done — in a footnote — but it’s there.”

The debate over autism was even more furious, and it resulted in a similar rapprochement.

From the outset, the committee intended to tighten the definition of autism and simplify it, eliminating related labels like Asperger syndrome and “pervasive developmental disorder not otherwise specified,” or PDD-NOS. The rate of diagnosis of such conditions has exploded over the past decade, in part due to the vagueness of the definitions, and the committee wanted to draw clearer boundaries.

It proposed a single “autism spectrum disorder” category, with stricter requirements.

Some outside researchers raised concerns. In January one of them, Dr. Fred Volkmar of the Yale School of Medicine, who had quit the committee in protest, presented research suggesting that 45 percent or more of people who currently had an autism or related diagnosis would not have one under the proposed revision.

Autism groups reacted immediately, fearing that the change in the diagnosis would deny services to children and families who need them.

The committee countered with its own study, suggesting that the new definition would exclude about 10 percent of people currently with a diagnosis. And again, the experts took a half step back.

The new, streamlined definition was approved, but with language that took into account a person’s diagnostic history. “It’s explicit that anyone who’s had an Asperger’s or autism or PDD-NOS diagnosis before is now included,” said Catherine Lord, a committee member who worked on the new definition and who is director of the Center for Autism and the Developing Brain in New York. “Essentially everyone gets in.”

Pediatric bipolar disorder posed a different challenge.

In the 1990s and 2000s, psychiatrists began giving aggressive, explosive children a diagnosis of bipolar disorder in increasing numbers. The trend appalled many patient advocates and doctors.

Bipolar disorder, which is characterized by episodes of depression and mania, had previously been an adult problem; now the diagnosis is given to children as young as 2 — along with powerful psychiatric drugs and tranquilizers that also cause rapid weight gain. The committee wanted to stop the trend in its tracks, said experts who were involved.

Most of the children treated for bipolar disorder did not have it, recent research found. The committee settled on an alternative label: “disruptive mood dysregulation disorder,” or D.M.D.D., which describes extreme hostility and outbursts beyond normal tantrums.

“They essentially wanted to have some place for these kids, and D.M.D.D. was all they had in their kit,” said Dr. Gabrielle Carlson, a child psychiatrist at Stony Brook University Medical Center, who provided some outside consultation. “These are mostly kids who have A.D.H.D. or what we would call oppositional defiant disorder, but with this explosive feature. They need help; you can’t wait forever. The question was what to call it, without pretending we know enough to saddle them with a lifelong diagnosis” like bipolar disorder.

D.M.D.D. has its own problems, as many experts were quick to point out. It could be a symptom of an underlying condition, as Dr. Carlson argues. It could “medicalize” frequent temper tantrums. It’s brand new, and no one knows how it will play out in practice.

But it is now in the book — because it was the best solution available, experts inside and outside of the revision process said.

From beginning to end, many experts said, the process of defining psychiatric diagnoses is very much like finding the right one for an individual: it’s a process of negotiation, in many cases.

“That’s one of the take-aways from all this, and I think it’s a good one,” Dr. Carlson said. “A diagnosis is a hypothesis. It’s a start, and you have to start somewhere. But that’s all it is.”

One of the committee’s most ambitious proposals was perhaps the least noticed: a commitment to update the book continually, when there’s good reason to, rather than once every decade or so in a giant heave. That was approved without much fanfare.

Read More..

DealBook: U.S. to Sell Last Holdings of A.I.G. Common Stock

The Treasury Department said on Monday that it planned to sell its remaining holdings of common stock in the American International Group, essentially ending taxpayers’ four-year ownership of the bailed-out insurer.

The Treasury Department said that it had begun a public offering of its 15.9 percent stake in A.I.G., amounting to about 234.2 million shares. It is the latest in a string of sales by the federal government, which has quickly reduced taxpayers’ holdings over the last two years.

All that would be left is a relatively small number of warrants that give the department the right to buy additional shares in A.I.G.

If completed, the sale would represent the achievement of a long-held goal of both the Obama administration and A.I.G. itself: ending the government’s ownership of the insurer. For the Treasury Department, it would signify a complete exit from perhaps the most controversial rescue struck during the financial crisis of 2008. In return for making up to $182 billion available to the company, the government received a stake that at its peak represented 92 percent of the company.

And for A.I.G., it would represent an unambiguous transformation into a fully private enterprise, an insurer that has clambered back from the brink of annihilation. Over the last four years, the company has sold off a number of assets in an effort to repay its bailout.

While the Treasury Department did not outline a timetable for its latest stock offering, the sale is expected to be completed quickly. Unlike in previous offerings, A.I.G. is not expected to buy back any of the shares being offered.

A spokesman for A.I.G. declined to comment.

The offering is being run by Bank of America Merrill Lynch, Citigroup, Deutsche Bank, Goldman Sachs and JPMorgan Chase.

Read More..

Fear of Fighting Haunts Once-Tranquil Damascus

Muzaffar Salman/Reuters

Damascenes cling to the hope that the ethnic strife that has deepened when fighting has reached other areas will not arise in their city.

DAMASCUS, Syria — Business has been terrible for Abu Tareq, a taxi driver, so last week, without telling his wife, he agreed to drive a man to the Damascus airport for 10 times the usual rate. But, he said later, he will not be doing that again.

On the airport road, he could hear the crash of artillery and the whiz of sniper fire. Dead rebels and soldiers lay on the roadsides. Abu Tareq saw a dog eating the body of a soldier.

“I will never forget this sight,” said Abu Tareq, 50, who gave only a nickname for safety reasons. “It is the road of the dead.”

Damascus, Syria’s capital, is one of the world’s oldest continuously inhabited cities, a touchstone of history and culture for the entire region. Through decades of political repression, the city preserved, at least on the surface, an atmosphere of tranquillity, from its wide downtown avenues to the spacious, smooth-stoned courtyard of the Umayyad Mosque and the vine-draped alleys of the Old City, where restaurants and bars tucked between the storehouses of medieval merchants hummed with quiet conversation.

Now, though, the rumble of distant artillery echoes through the city, and its residents are afraid to leave their neighborhoods. Cocooned behind rows of concrete blocks that close off routes to the center, they huddle in fear of a prolonged battle that could bring destruction and division to a place where secular and religious Syrians from many sects — Sunni, Shiite, Alawite, Christian and others — have long lived peacefully.

For more than a week, Syrian rebels and government forces have fought for the airport road, as the military tries to seal off the capital city, the core of President Bashar al-Assad’s power, from a semicircle of rebellious suburbs. Rebels have now kept the pressure on the government for as long as they did during their previous big push toward Damascus last summer. This time, improved supply lines and tactics, some rebels and observers say, may provide a more secure foothold.

But the security forces wield overwhelming firepower, and while it has been unable to subdue the suburbs, some rebel fighters say they lack the intelligence information, arms and communication to advance. That raises the specter of a destructive standoff like the one that has devastated the commercial hub of Aleppo.

“Damascus was the city of jasmine,” Mahmoud, 40, a public-school teacher, said in an interview in the capital. “It is not the city I knew just a few weeks ago.”

Car bombs have ripped through neighborhoods, their targets and perpetrators only guessed at. Checkpoints choke traffic, turning 20-minute jaunts into three-hour ordeals. Wealthy residents find it quicker and safer to drive to Beirut, Lebanon, for a weekend trip than to the Old City.

Shells have been fired from Mount Qasioun overlooking Damascus, a favorite destination from which to admire the city’s sparkling lights. West of downtown, where the palace stands on a plateau, things are relatively quiet. But from the mountain, puffs of smoke can now be seen over suburbs in an arc from northeast to southwest.

Mahmoud, unable to find heating oil and medicine for his sick wife, said his grocer has lectured him daily on shortages and soaring prices. The once-ubiquitous government, he said, now appears to have no role beyond flooding streets with soldiers and security officers, “who are sometimes good and sometimes rude.”

People with roots in other towns have left, he said, “but what about me, who is a Damascene, and has no other city?”

The sense of claustrophobia has grown as rebels have declared the airport a legitimate target and the government has blocked Baghdad Street, a main avenue out of the city. On Sunday, it blocked the highway south to Dara’a.

In some outlying neighborhoods and nearby suburbs, the front lines seem to be hardening.

On the route into Qaboun, a neighborhood less than two miles from the center of Damascus, the last government checkpoint in recent days was near the municipal building. Less than a quarter-mile on, rebels controlled the area around the Grand Mosque.

An employee of The New York Times reported from Damascus, Syria, and Anne Barnard from Beirut, Lebanon. Neil MacFarquhar contributed reporting from Beirut.

Read More..

Browser Wars Flare Again, This Time for Phones and Tablets

SAN FRANCISCO — When Google took a video camera to Times Square in 2009 and asked passers-by what a browser is, most of the answers were hilariously incorrect, from “a search engine” to “broadband” to “Yahoo.”

But even if consumers are not so sure what Web browsers are (programs like Internet Explorer and Firefox), they have become a crucial business for tech companies like Google and Microsoft. That is because they are now the entry point not just to the Web but to everything stored online, like Web apps, documents and photos.

And as the cloud grows more integral, both for businesses and people, the browser companies are engaged in a new battle to win our allegiance that will affect how we use the Internet.

It’s an echo of the so-called browser wars of the 1990s, when Internet Explorer and Netscape Navigator fought for dominance on the personal computer. This time, though, the struggle is shaping up to be over which company will control the mobile world — with browsers on smartphones and tablets. Entrenched businesses are at stake. Google’s browser-based business apps, for instance, threaten Microsoft’s desktop software, and mobile Web apps threaten Apple’s App Store.

“Twenty years ago, we didn’t know how the Internet was going to get used by people, and we for sure didn’t know about mobile or tablets,” said Marc Andreessen, co-founder of the first major browser, Netscape Navigator, and an investor in Rockmelt, a browser start-up. “Mobile is a whole new level of reinvention, so it feels like we’re in the most fertile time of invention since the early ’90s.”

Browsers give Web companies more control over how people use their products, and data about how people use the Web, which they can use to improve their products and inform advertisers. Faster browsing leads to more Web activity, which in turns leads to more revenue for Web companies — whether searching on Google or shopping on Amazon.com, which built a Kindle browser, Silk.

As Mr. Andreessen put it, “Why let something be between us and our users? Let’s have as much control of the user experience as we can have; make sure our services are wired in.”

Google’s Chrome browser, for example, makes Google searches faster and simpler because people can enter search queries directly into the address bar. And its apps — like Gmail, Drive for file storage and Docs for word processing — are all accessible through any browser.

“Chrome makes it much easier for you to search, browse the Web and use Drive, Docs and apps, and we are fortunate to be in a position where when people do those things, we do better,” said Sundar Pichai, senior vice president of Chrome at Google. “Chrome is a platform, the underlying layer on which all our cloud operations run.”

Most people use either Chrome, Microsoft’s Internet Explorer, Mozilla’s Firefox or Apple’s Safari. In the biggest disruption to the market in 15 years, Chrome last spring toppled Internet Explorer as the most popular browser in the world, despite the fact that it does not come loaded on computers as Explorer and Safari do. It now has 36 percent of the global market, while Internet Explorer’s share has dived to 31 percent, according to StatCounter, which tracks browser market share.

A host of smaller companies, like Rockmelt and Opera, are also trying to grab market share, largely by focusing on mobile devices.

Browsers themselves are not lucrative businesses. Some, like Firefox, earn money from search engines like Google and Microsoft’s Bing that pay when people use the search bar built in to the browser.

“No one is doing a browser to make money,” said David B. Yoffie, a professor at Harvard Business School who was co-author of a book about the first browser wars. “Suddenly now, the browser has become the interface for the cloud more broadly, not just for traditional Web sites.”

In their search for dollars, browser companies are redesigning their products to follow consumers to mobile devices, social networks and cloud-based apps.

For example, new mobile browsers let people swipe through tabs with their fingers, automatically resize or zoom in on Web pages so they fit a phone’s screen and load pages faster than older mobile browsers. Some also sync with other devices, so things like most-visited Web sites, passwords and credit card numbers are available everywhere.

Nonetheless, browsing the Web on a mobile device is still inferior to using the desktop Web or smartphone apps. Apps, like those downloaded from Apple’s App Store and Google Play for Android devices, have more exciting features, are faster to load and are better optimized to small screens.

Read More..

A Breakthrough Against Leukemia Using Altered T-Cells

PHILIPSBURG, Pa. — Emma Whitehead has been bounding around the house lately, practicing somersaults and rugby-style tumbles that make her parents wince.

It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options.

Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the AIDS virus to reprogram Emma’s immune system genetically to kill cancer cells.

The treatment very nearly killed her. But she emerged from it cancer-free, and seven months later is still in complete remission. She is the first child and one of the first humans ever in whom new techniques have achieved a long-sought goal — giving a patient’s own immune system the lasting ability to fight cancer.

Emma had been ill with acute lymphoblastic leukemia since 2010, when she was 5, her parents, Kari and Tom, said. She is their only child.

She is among just a dozen patients with advanced leukemia to have received the experimental treatment, which was developed at the University of Pennsylvania. Similar approaches are also being tried at other centers, including the National Cancer Institute and Memorial Sloan-Kettering Cancer Center in New York.

“Our goal is to have a cure, but we can’t say that word,” said Dr. Carl June, who leads the research team at the University of Pennsylvania. He hopes the new treatment will eventually replace bone-marrow transplantation, an even more arduous, risky and expensive procedure that is now the last hope when other treatments fail in leukemia and related diseases.

Three adults with chronic leukemia treated at the University of Pennsylvania have also had complete remissions, with no signs of disease; two of them have been well for more than two years, said Dr. David Porter. Four adults improved but did not have full remissions, and one was treated too recently to evaluate. A child improved and then relapsed. In two adults, the treatment did not work at all. The Pennsylvania researchers are presenting their results on Sunday and Monday in Atlanta at a meeting of the American Society of Hematology.

Despite the mixed results, cancer experts not involved with the research say it has tremendous promise, because even in this early phase of testing it has worked in seemingly hopeless cases.

“I think this is a major breakthrough,” said Dr. Ivan Borrello, a cancer expert and associate professor of medicine at the Johns Hopkins University School of Medicine.

Dr. John Wagner, director of pediatric blood and marrow transplantation at the University of Minnesota, called the Pennsylvania results “phenomenal,” and said they were “what we’ve all been working and hoping for but not seeing to this extent.”

A major drug company, Novartis, is betting on the Penn team, and has committed $20 million to building a research center on the Penn campus to bring the treatment to market.

Hervé Hoppenot, president of Novartis Oncology, called the research “fantastic” and said it had the potential — if the early results hold up — to revolutionize the treatment of leukemia and related blood cancers. Researchers say the same approach, reprogramming the patient’s immune system, may also be used eventually against tumors like breast and prostate cancer.

To perform the treatment, doctors remove millions of the patient’s T-cells — a type of white blood cell — and insert new genes that enable the T-cells to kill cancer cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turns malignant in leukemia.

The altered T-cells — called chimeric antigen receptor cells — are then dripped back into the patient’s veins, and if all goes well they multiply like crazy and start destroying the cancer.

The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells, whether they are healthy or malignant.

A sign that the treatment is working is that the patient becomes terribly ill, with raging fevers and chills — a reaction that oncologists call “shake and bake,” Dr. June said. Its medical name is cytokine-release syndrome, or cytokine storm, referring to the natural chemicals that pour out of cells in the immune system as they are being activated, causing fevers and other symptoms. The storm can also flood the lungs and cause perilous drops in blood pressure — effects that nearly killed Emma.

Steroids sometimes ease the reaction, but did not help Emma. Her temperature hit 105. She wound up on a ventilator, unconscious and swollen almost beyond recognition, surrounded by friends and family who had come to say goodbye.

But at the eleventh hour, a battery of blood tests gave the researchers a clue as to what might help save Emma: Her level of one of the cytokines, interleukin-6 or IL-6, had shot up a thousandfold. Doctors had never seen such a spike before and thought it might be what was making her so sick. Dr. June knew that a drug could lower IL-6 — his daughter takes it, for rheumatoid arthritis. It had never been used for a crisis like Emma’s, but there was little to lose. Her oncologist, Dr. Stephan A. Grupp, ordered the drug. The response, he said, was “amazing.”

Within hours, Emma began to stabilize. She woke up a week later, on May 2, the day she turned 7; the intensive-care staff sang “Happy Birthday.”

Since then, the research team has used the same drug, tocilizumab, in several other patients.

Read More..

A Breakthrough Against Leukemia Using Altered T-Cells

PHILIPSBURG, Pa. — Emma Whitehead has been bounding around the house lately, practicing somersaults and rugby-style tumbles that make her parents wince.

It is hard to believe, but last spring Emma, then 6, was near death from leukemia. She had relapsed twice after chemotherapy, and doctors had run out of options.

Desperate to save her, her parents sought an experimental treatment at the Children’s Hospital of Philadelphia, one that had never before been tried in a child, or in anyone with the type of leukemia Emma had. The experiment, in April, used a disabled form of the AIDS virus to reprogram Emma’s immune system genetically to kill cancer cells.

The treatment very nearly killed her. But she emerged from it cancer-free, and seven months later is still in complete remission. She is the first child and one of the first humans ever in whom new techniques have achieved a long-sought goal — giving a patient’s own immune system the lasting ability to fight cancer.

Emma had been ill with acute lymphoblastic leukemia since 2010, when she was 5, her parents, Kari and Tom, said. She is their only child.

She is among just a dozen patients with advanced leukemia to have received the experimental treatment, which was developed at the University of Pennsylvania. Similar approaches are also being tried at other centers, including the National Cancer Institute and Memorial Sloan-Kettering Cancer Center in New York.

“Our goal is to have a cure, but we can’t say that word,” said Dr. Carl June, who leads the research team at the University of Pennsylvania. He hopes the new treatment will eventually replace bone-marrow transplantation, an even more arduous, risky and expensive procedure that is now the last hope when other treatments fail in leukemia and related diseases.

Three adults with chronic leukemia treated at the University of Pennsylvania have also had complete remissions, with no signs of disease; two of them have been well for more than two years, said Dr. David Porter. Four adults improved but did not have full remissions, and one was treated too recently to evaluate. A child improved and then relapsed. In two adults, the treatment did not work at all. The Pennsylvania researchers are presenting their results on Sunday and Monday in Atlanta at a meeting of the American Society of Hematology.

Despite the mixed results, cancer experts not involved with the research say it has tremendous promise, because even in this early phase of testing it has worked in seemingly hopeless cases.

“I think this is a major breakthrough,” said Dr. Ivan Borrello, a cancer expert and associate professor of medicine at the Johns Hopkins University School of Medicine.

Dr. John Wagner, director of pediatric blood and marrow transplantation at the University of Minnesota, called the Pennsylvania results “phenomenal,” and said they were “what we’ve all been working and hoping for but not seeing to this extent.”

A major drug company, Novartis, is betting on the Penn team, and has committed $20 million to building a research center on the Penn campus to bring the treatment to market.

Hervé Hoppenot, president of Novartis Oncology, called the research “fantastic” and said it had the potential — if the early results hold up — to revolutionize the treatment of leukemia and related blood cancers. Researchers say the same approach, reprogramming the patient’s immune system, may also be used eventually against tumors like breast and prostate cancer.

To perform the treatment, doctors remove millions of the patient’s T-cells — a type of white blood cell — and insert new genes that enable the T-cells to kill cancer cells. The new genes program the T-cells to attack B-cells, a normal part of the immune system that turns malignant in leukemia.

The altered T-cells — called chimeric antigen receptor cells — are then dripped back into the patient’s veins, and if all goes well they multiply like crazy and start destroying the cancer.

The T-cells home in on a protein called CD-19 that is found on the surface of most B-cells, whether they are healthy or malignant.

A sign that the treatment is working is that the patient becomes terribly ill, with raging fevers and chills — a reaction that oncologists call “shake and bake,” Dr. June said. Its medical name is cytokine-release syndrome, or cytokine storm, referring to the natural chemicals that pour out of cells in the immune system as they are being activated, causing fevers and other symptoms. The storm can also flood the lungs and cause perilous drops in blood pressure — effects that nearly killed Emma.

Steroids sometimes ease the reaction, but did not help Emma. Her temperature hit 105. She wound up on a ventilator, unconscious and swollen almost beyond recognition, surrounded by friends and family who had come to say goodbye.

But at the eleventh hour, a battery of blood tests gave the researchers a clue as to what might help save Emma: Her level of one of the cytokines, interleukin-6 or IL-6, had shot up a thousandfold. Doctors had never seen such a spike before and thought it might be what was making her so sick. Dr. June knew that a drug could lower IL-6 — his daughter takes it, for rheumatoid arthritis. It had never been used for a crisis like Emma’s, but there was little to lose. Her oncologist, Dr. Stephan A. Grupp, ordered the drug. The response, he said, was “amazing.”

Within hours, Emma began to stabilize. She woke up a week later, on May 2, the day she turned 7; the intensive-care staff sang “Happy Birthday.”

Since then, the research team has used the same drug, tocilizumab, in several other patients.

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As Recovery Inches Ahead, Banks Face a New Reckoning

The nation’s largest banks are facing a fresh torrent of lawsuits asserting that they sold shoddy mortgage securities that imploded during the financial crisis, potentially adding significantly to the tens of billions of dollars the banks have already paid to settle other cases.

Regulators, prosecutors, investors and insurers have filed dozens of new claims against Bank of America, JPMorgan Chase, Wells Fargo, Citigroup and others, related to more than $1 trillion worth of securities backed by residential mortgages.

Estimates of potential costs from these cases vary widely, but some in the banking industry fear they could reach $300 billion if the institutions lose all of the litigation. Depending on the final price tag, the costs could lower profits and slow the economic recovery by weakening the banks’ ability to lend just as the housing market is showing signs of life.

The banks are battling on three fronts: with prosecutors who accuse them of fraud, with regulators who claim that they duped investors into buying bad mortgage securities, and with investors seeking to force them to buy back the soured loans.

“We are at an all-time high for this mortgage litigation,” said Christopher J. Willis, a lawyer with Ballard Spahr.

Efforts by the banks to limit their losses could depend on the outcome of one of the highest-stakes lawsuits to date — the $200 billion case that the Federal Housing Finance Agency, which oversees the housing twins Fannie Mae and Freddie Mac, filed against 17 banks last year, claiming that they duped the mortgage finance giants into buying shaky securities.

Last month, lawyers for some of the nation’s largest banks descended on a federal appeals court in Manhattan to make their case that the agency had waited too long to sue. A favorable ruling could overturn a decision by Judge Denise L. Cote, who is presiding over the litigation and has so far rejected virtually every defense raised by the banks, and would be cheered in bank boardrooms. It could also allow the banks to avoid federal housing regulators’ claims.

At the same time, though, some major banks are hoping to reach a broad settlement with housing agency officials, according to several people with knowledge of the talks. Although the negotiations are at a very tentative stage, the banks are broaching a potential cease-fire.

As the housing market and the nation’s economy slowly recover from the 2008 financial crisis, Wall Street is vulnerable on several fronts, including tighter regulations assembled in the aftermath of the crisis and continuing investigations into possible rigging of a major international interest rate. But the mortgage lawsuits could be the most devastating and expensive, bank analysts say.

“All of Wall Street has essentially refused to deal with the real costs of the litigation that they are up against,” said Christopher Whalen, a senior managing director at Tangent Capital Partners. “The real price tag is terrifying.”

Anticipating painful costs from mortgage litigation, the five major sellers of mortgage-backed securities set aside $22.5 billion as of June 30 just to cushion themselves against demands that they repurchase soured loans from trusts, according to an analysis by Natoma Partners.

But in the most extreme situation, the litigation could empty even more well-stocked reserves and weigh down profits as the banks are forced to pay penance for the subprime housing crisis, according to several senior officials in the industry.

There is no industrywide tally of how much banks have paid since the financial crisis to put the mortgage litigation behind them, but analysts say that future settlements will dwarf the payouts so far. That is because banks, for the most part, have settled only a small fraction of the lawsuits against them.

JPMorgan Chase and Credit Suisse, for example, agreed last month to settle mortgage securities cases with the Securities and Exchange Commission for $417 million, but still face billions of dollars in outstanding claims.

Bank of America is in the most precarious position, analysts say, in part because of its acquisition of the troubled subprime lender Countrywide Financial.

Last year, Bank of America paid $2.5 billion to repurchase troubled mortgages from Fannie Mae and Freddie Mac, and $1.6 billion to Assured Guaranty, which insured the shaky mortgage bonds.

But in October, federal prosecutors in New York accused the bank of perpetrating a fraud through Countrywide by churning out loans at such a fast pace that controls were largely ignored. A settlement in that case could reach well beyond $1 billion because the Justice Department sued the bank under a law that could allow roughly triple the damages incurred by taxpayers.

Bank of America’s attempts to resolve some mortgage litigation with an umbrella settlement have stalled. In June 2011, the bank agreed to pay $8.5 billion to appease investors, including the Federal Reserve Bank of New York and Pimco, that lost billions of dollars when the mortgage securities assembled by the bank went bad. But the settlement is in limbo after being challenged by investors. Kathy D. Patrick, the lawyer representing investors, has said she will set her sights on Morgan Stanley and Wells Fargo next.

Of the more than $1 trillion in troubled mortgage-backed securities remaining, Bank of America has more than $417 billion from Countrywide alone, according to an analysis of lawsuits and company filings. The bank does not disclose the volume of its mortgage litigation reserves.

“We have resolved many Countrywide mortgage-related matters, established large reserves to address these issues and identified a range of possible losses beyond those reserves, which we believe adequately addresses our exposures,” said Lawrence Grayson, a spokesman for Bank of America.

Adding to the legal fracas, the New York attorney general, Eric T. Schneiderman, accused Credit Suisse last month of perpetrating an $11.2 billion fraud by deceiving investors into buying shoddy mortgage-backed securities. According to the complaint, the bank dismissed flaws in the loans packaged into securities even while assuring investors that the quality was sound. The bank disputes the claims.

It is the second time that Mr. Schneiderman — who is also co-chairman of the Residential Mortgage-Backed Securities Working Group, created by President Obama in January — has taken aim at Wall Street for problems related to the subprime mortgage morass. In October, he filed a civil suit in New York State Supreme Court against Bear Stearns & Company, which JPMorgan Chase bought in 2008. The complaint claims that Bear Stearns and its lending unit harmed investors who bought mortgage securities put together from 2005 through 2007. JPMorgan denies the allegations.

Another potentially costly headache for the banks are the demands from a number of private investors who want the banks to buy back securities that violated representations and warranties vouching for the loans.

JPMorgan Chase told investors that as of the second quarter of this year, it was contending with more than $3.5 billion in repurchase demands. In the same quarter, it received more than $1.5 billion in fresh demands. Bank of America reported that as of the second quarter, it was dealing with more than $22 billion in unresolved demands, more than $8 billion of which were received during that quarter.

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Shintaro Ishihara, Right-Wing Japanese Politician, Makes Gains

TOKYO — Shintaro Ishihara has been a rare, flamboyant presence in Japan’s otherwise drab political world for half a century. A novelist turned right-wing firebrand, he has long held celebrity status on the political margins, where he was known for dramatic flourish. He once signed a pact in blood to oppose diplomatic ties with China because of its communist government, and he published a book at the height of Japan’s economic power that lectured his countrymen on the need to end what he considered its postwar servility to the United States.

Now, at 80, Mr. Ishihara is leading a newly formed populist party and has emerged as a contender for prime minister, vowing to turn Japan into a more independent, possibly nuclear-armed nation. While political analysts deem him a long shot, they say the fact that he has gotten this far after decades of pushing what was seen as a fringe agenda is a worrying sign of how desperate this nation is for strong leadership after years of cascading troubles.

With his promises to restore Japan’s battered national pride, Mr. Ishihara has staked out an even more stridently nationalistic position than the current front-runner, Shinzo Abe, the leader of the conservative Liberal Democratic Party, who has called for revising Japan’s pacifist constitution. Analysts worry that if Mr. Ishihara succeeds in his bid to become prime minister, he could weaken relations with the United States, yank Japan to the right and damage ties with China, which is already angered by his almost single-handedly rekindling a territorial dispute over an island chain.

But even in the likely event that Mr. Ishihara loses, they say, his campaign could still have a lasting effect, bringing patriotic populism into the political mainstream of a nation that has shunned such open jingoism since its devastating defeat in World War II.

“This election will be a test of whether Japan is really losing its dovishness,” said Takeshi Sasaki, a politics professor at Gakushuin University in Tokyo. “There is so much irritation at how everything seems to be going wrong, and Japan is losing its pride. Politicians on the right like Ishihara and Abe are trying to fan these flames.”

The rise of the two hard-liners has already contributed to hand-wringing among liberals who are anxious that the foreboding sense that Japan is fast becoming an international has-been has left the Japanese vulnerable to long-suppressed nationalism. Even those who call those fears overblown acknowledge that anti-China feelings, which could be easily exploited, are rising as that country eclipses Japan, builds a formidable military and makes its territorial ambitions clear.

From Mr. Ishihara’s vantage point, those geopolitical realities make now the perfect time for Japan to put him in charge.

“Here I am, the old man who has run amok!” he bellowed to a wave of applause at a recent campaign appearance in front of Shinjuku train station in Tokyo. “I am 80 years old, and I am standing here because I want to break through the indecisive and barren politics that is stifling Japan!”

A tall, bespectacled figure, Mr. Ishihara spent most of his short speech emphasizing what has become the central campaign message of his Japan Restoration Party: offering forceful leadership to end Japan’s long political drift by breaking the grip of bureaucrats and vested interests.

Much of the party’s message, however, has become vintage Ishihara. He goes further than Mr. Abe, calling for an outright scrapping of Japan’s antiwar constitution, written by its postwar American occupiers. He still speaks about ending what he sees as political and cultural subservience to the United States and pledges to resist Chinese territorial appetites, promising to build permanent structures on the disputed islands in a move likely to further antagonize China.

“I cannot allow myself to die until my Japan, which has been made a fool of by China, and seduced as a mistress by the United States, is able to stand up again as a stronger, more beautiful nation,” Mr. Ishihara said last month to reporters, explaining why he resigned after 13 years as Tokyo’s governor to return to national politics. He did so after being asked to lead the fledgling Restoration Party’s slate in this month’s parliamentary election by its founder, the popular mayor of Osaka who did not yet want to run for national office.

So far, polls show that Mr. Ishihara has only limited appeal. His party’s approval ratings are in the low teens, about the same as the unpopular incumbent Democratic Party, but below Mr. Abe’s Liberal Democrats, who poll only slightly better, at around 20 percent. Polls also show that more than half of voters disapprove of Mr. Ishihara and of scrapping the antiwar clause of Japan’s constitution.

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You for Sale: Company Envisions ‘Vaults’ for Personal Data

Peter DaSilva for The New York Times

Michael Fertik, the founder and chief executive of Reputation.com, at its offices in Redwood City, Calif., where he has amassed a database of information collected on millions of consumers.

“YOU are walking around naked on the Internet and you need some clothes,” says Michael Fertik. “I am going to sell you some.”

Naked? Not exactly, but close.

Mr. Fertik, 34, is the chief executive of Reputation.com, a company that helps people manage their online reputations. From his perch here in Silicon Valley, he views the digital screens in our lives, the smartphones and the tablets, the desktops and the laptops, as windows of a house. People go about their lives on the inside, he says, while dozens of marketing and analytics companies watch through the windows, sizing them up like peeping Toms.

By now many Americans are learning that they are living in a surveillance economy. “Information resellers,” also known as “data brokers,” have collected hundreds to thousands of details — what we buy, our race or ethnicity, our finances and health concerns, our Web activities and social networks — on almost every American adult. Other companies that specialize in ranking consumers use computer algorithms to covertly score Internet users, identifying some as “high-value” consumers worthy of receiving pitches for premium credit cards and other offers, while dismissing others as a waste of time and marketing money. Yet another type of company, called an ad-trading platform, profiles Internet users and auctions off online access to them to marketers in a practice called “real-time bidding.”

As these practices have come to light, several members of Congress, and federal agencies, have opened investigations.

At least for now, however, these companies typically do not permit consumers to see the records or marketing scores that have been compiled about them. And that is perfectly legal.

Now, Mr. Fertik, the loquacious, lion-maned founder of Reputation.com, says he has the free-market solution. He calls it a “data vault,” or “a bank for other people’s data.”

Here at Reputation.com’s headquarters, a vast open-plan office decorated with industrial-looking metal struts and reclaimed wood — a discreet homage to the lab where Thomas Edison invented the light bulb — his company has amassed a database on millions of consumers. Mr. Fertik plans to use it to sell people on the idea of taking control of their own marketing profiles. To succeed, he will have to persuade people that they must take charge of their digital personas.

Pointing out the potential hazards posed by data brokers and the like is part of Mr. Fertik’s M.O. Covert online profiling and scoring, he says, may unfairly exclude certain Internet users from marketing offers that could affect their financial, educational or health opportunities — a practice Mr. Fertik calls “Weblining.” He plans to market Reputation.com’s data vault, scheduled to open for business early next year, as an antidote.

“A data privacy vault,” he says, “is a way to control yourself as a person.”

Reputation.com is at the forefront of a nascent industry called “personal identity management.” The company’s business model for its vault service involves collecting data about consumers’ marketing preferences and giving them the option to share the information on a limited basis with certain companies in exchange for coupons, say, or status upgrades. In turn, participating companies will get access both to potential customers who welcome their pitches and to details about the exact products and services those people are seeking. In theory, the data vault would earn money as a kind of authorization supervisor, managing the permissions that marketers would need to access information about Reputation.com’s clients.

To some, the idea seems a bit quixotic.

Reputation.com, with $67 million in venture capital, is not making a profit. Although the company’s “privacy” products, like removing clients’ personal information from list broker and marketing databases, are popular, its reputation management techniques can be controversial. For instance, it offers services meant to make negative commentary about individual or corporate clients less visible on the Web.

And there are other hurdles, like competition. A few companies, like Personal, have already introduced vault services. Also, a number of other enterprises have tried — and quickly failed — to sell consumers on data lockers.

Even so, Mr. Fertik contends Reputation.com has the answer. The company already has several hundred thousand paying customers, he says, and patents on software that can identify consumers’ information online and score their reputations. He intends to show clients their scores and advise them on how to improve them.

“You can’t just build a vault and wish that vendors cared enough about your data to pay for it,” Mr. Fertik says. “You have to build a business that gives you the lift to accumulate a data set and attract consumers, the science to create insights that are valuable to vendors, and the power to impose restrictions on the companies who consume your data.”

THE consumer data trade is large and largely unregulated.

Companies and organizations in the United States spend more than $2 billion a year on third-party data about individuals, according to a report last year on personal identity management from Forrester Research, a market research firm. They spend billions more on credit data, market research and customer data analytics, the report said.

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