Sunday, September 30, 2007

Alzheimer's: Sarah Polley's Movie Away From Her - Directors Guild of Canada Award

Sarah Polley's movie won a Canadian film award this weekend:

From the CBC:

Polley's film big winner at Director's Guild Awards
Last Updated: Sunday, September 30, 2007 | 9:38 AM ET
The Canadian Press

Sarah Polley's poignant Away From Her was the big winner at the 2007 Directors Guild of Canada Awards on Saturday.

The film was honoured as best picture, and Polley was named best director; her husband, David Wharnsby, won the prize for best picture editing.

The critically acclaimed movie chronicles the intrusion of Alzheimer's disease into the lives of an aging couple, played by Gordon Pinsent and Julie Christie.

[ ... Read the full article ... ]

Read my earlier post about this movie here.

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Friday, September 28, 2007

60-Second Psych and 60-Second Lectures

Scientific American has created a courtesy weekly podcast to highlight research about the brain and behavior.

The podcast can be accessed at this webpage: Scientific American webpage.

Not a bad way to spend a minute! Which, by the way, reminds me to mention that if you are in Philadelphia, the University of Pennsylvania still has several of its outdoors 60-second lectures remaining over the next few weeks, which are always fun to attend!

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Office of Inspector General Report on FDA Oversight of Clinical Trials

Available in a .pdf document from the "What's New" page of the OIG website here: Link for OIG webpage.

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Thursday, September 27, 2007

Donald Stein's Research: Recovery from Traumatic Brain Injury (TBI)

Yesterday's Wall Street Journal ran a feature article about neuroscientist Donald Stein and his career exploring facets of recovery from traumatic brain injury (TBI):

One Doctor's Lonely Quest To Heal Brain Injury
After 40 Years, Skeptics Back Hormone Therapy; Experiments in a Trailer
By THOMAS M. BURTON
September 26, 2007; Page A1

[snip]

Dr. Stein still wanted to figure out why those brain-injured rats seemed to recover. But he says he concluded that he wouldn't win tenure if he pursued the question.

In 1966, with a wife and young child to support, he left MIT to take a job as a psychology professor and director of the brain-research lab at Clark University in Worcester, Mass.

His growing interest in the possibility of recovery from brain injury put him in a tiny minority. Most neurologists at the time still agreed with Nobel laureate Santiago Ramón y Cajal, who wrote in 1913, "In the adult brain, nervous pathways are fixed and immutable. Everything may die, nothing may be regenerated."

Starting in the late 1960s, Dr. Stein began publishing research that suggested the Nobel winner was wrong.

His lab began methodically studying precisely why some rats stayed smart despite injury. The researchers would place rats in a large vat of water. The rats had to swim to reach a safe platform in a test called a "water maze." Then the scientists surgically damaged the animals' brains to study what happened after injury: Would they still be able to maneuver through the maze? The rats that recovered quickly were all female, although not all of the females recovered.

Dr. Stein considered whether the explanation might be something complex, like molecular or genetic differences between males and females. But investigating that would take much more time and money than seeing if a female hormone might yield some clues. First his team evaluated estrogen, but didn't find a major correlation. Then they tried progesterone -- a female hormone that helps protect fetuses from injury during pregnancy.

In these early experiments, Dr. Stein tested female rats to see if they would recover better or worse at different times during their hormonal cycles that resemble human menstruation. Progesterone levels rise and fall during these cycles, and these early studies did indeed show that female rats that were high in progesterone recovered faster.

Dr. Stein thought he had a big part of the answer to the question that had been vexing him for years. The medical establishment, however, largely shrugged off the results.

[snip]

[ ... Read the article ... ]

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Neurodegenerative Diseases: Progranulin (PGRN) Mutation and TDP-43

From a National Institutes of Health (NIH) press release on the 26th:

Scientists Suggest New Pathway Causing Cell Death in Dementia

Scientists have discovered a link between a mutated gene and a protein found in dead brain cells of people who suffer from a form of dementia and other neurological disorders. The finding, reported in the Sep. 26, 2007, issue of the Journal of Neuroscience, demonstrates for the first time a pathological pathway that ultimately results in cell death related to frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). The discovery could eventually play a role in the design of new drug therapies. The study was funded by the National Institute on Aging (NIA) at the National Institutes of Health (NIH).

Leonard Petrucelli, Ph.D., and Dennis W. Dickson, M.D, of the Mayo Clinic in Jacksonville, Fla., led the international team of scientists in the study supported by the Mayo Clinic Foundation.

The study, in cell cultures, showed that a cell death pathway is involved. A cascade of events begins with a mutation in the gene progranulin (PGRN) located on chromosome 17. Normally, high levels of PGRN exist in a cell to promote cell growth and survival. But when progranulin gene mutations occur, low levels of PGRN result. The investigators showed that this causes a protein called TDP-43 to be cut into two fragments. These fragments then migrate from their usual location in the nucleus into the surrounding cytoplasm of the cell where they form inclusions, or insoluble clumps of protein. This abnormal process results in the neurodegeneration in people with FTD and ALS.

"This research defines a novel disease mechanism that may be important in a number of age-related neurological diseases," said Marcelle Morrison-Bogorad, Ph.D., Director of the Neuroscience and Neuropsychology Program at the NIA. "It opens a window on possible future applications, from approaches to novel therapeutic targets to the continued exploration of cell survival systems."

[ ... Read the full press release ... ]

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Wednesday, September 26, 2007

Neuropsychology Abstract of the Day: Alzheimer's Disease (AD), fMRI, and Cognition

Diamond EL, Miller S, Dickerson BC, Atri A, Depeau K, Fenstermacher E, Pihlajamäki M, Celone K, Salisbury S, Gregas M, Rentz D, & Sperling RA. Relationship of fMRI activation to clinical trial memory measures in Alzheimer disease. Neurology. 2007 Sep 25; 69(13): 1331-1341.

Memory Disorders Unit, Brigham and Women’s Hospital, 221 Longwood Ave, Boston, MA 02115

BACKGROUND: Functional MRI (fMRI) has shown promise as a tool to characterize altered brain function in Alzheimer disease (AD) and for use in proof of concept clinical trials. FMRI studies of subjects with AD have demonstrated altered hippocampal and neocortical activation while encoding novel stimuli compared to older controls. However, the relationship between fMRI activation and performance on standardized clinical trial memory measures has not been fully investigated. OBJECTIVE: To determine whether patterns of activation during an associative-memory fMRI paradigm correlate with performance on memory measures used in AD clinical trials. METHODS: Twenty-nine subjects with AD underwent neuropsychological testing, including the AD Assessment Scale (ADAS-Cog), and an associative-encoding fMRI paradigm. Scores were entered as regressors in SPM2 analyses of the differential fMRI activation to novel-vs-repeated (NvR) stimuli. To account for cerebral atrophy, native-space structure-function analyses were performed with subjects' high-resolution structural images. RESULTS: Performance on the ADAS-Cog verbal memory component, and the ADAS-Cog total score, correlated with NvR activation in left superior temporal (p = 0.0003; r = -0.51) and left prefrontal (p = 0.00001; r = -0.63) cortices. In a subgroup with more extensive neuropsychological testing (n = 14), performance on the Free and Cued Selective Reminding Test was correlated with activation in these same regions. fMRI activation remained correlated with performance even when accounting for atrophy. CONCLUSIONS: The relationship between functional MRI (fMRI) activation and standardized memory measures supports the potential use of fMRI to investigate regional mechanisms of treatment response in clinical trials of novel therapies for Alzheimer disease. GLOSSARY: AD = Alzheimer disease; ADAS-Cog = AD Assessment Scale; EPI = echoplanar imaging sequence; FA = flip angle; FCSRT = Free and Cued Selective Reminding Test; FLAME = FMRIB's Local Analysis of Mixed Effects; fMRI = Functional MRI; FOV = field of view; GLM = general linear model; HRF = hemodynamic response function; LFG = left fusiform gyrus; LPFC = left prefrontal cortex; LSTG = left superior temporal gyrus; MMSE = Mini-Mental State Examination; MTL = medial temporal lobe; NvR = novel-vs-repeated; ROI = region of interest; TE = echo time; TR = repetition time.

PMID: 17893294 [PubMed - as supplied by publisher]

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Tuesday, September 25, 2007

MacArthur Fellows: Yoky Matsuoka, A Neurorobotics Expert, Becomes One

Congratulations to Yoky Matsuoka for becoming a MacArthur Fellow. She is an Associate Professor in the Department of Computer Science and Engineering at the University of Washington, Seattle.

Read about her work in rehabilitation neurorobotics.

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Saturday, September 22, 2007

Alzheimer's: Sarah Polley's Movie, Away From Her


From Australia's National Nine News:

Alzheimer's struggle brought to screen
Friday Sep 21 08:19 AEST

At just 28 years of age, Canadian director Sarah Polley has made a debut feature film that directors twice her age and experience would be proud of.

Also a talented actress, she is best known to Australian audiences for her acting roles as a supermarket checkout chick in the 1999 crime thriller Go and a schoolgirl in Atom Egoyan's The Sweet Hereafter.

For her directorial debut, Away From Her, Polley chose to tell the story of a couple in their 60s who are dealing with Alzheimer's disease.

It is hardly a film you would expect a 20-something film-maker to produce.

The fact that she convinced Oscar winners Julie Christie and Olympia Dukakis to be part of the movie is even more impressive.

"During rehearsals, all of a sudden it dawned on me that I was directing people who were twice my age, and who had a good deal more experience than I did, and who were actors that I have grown up in awe of," Polley told AAP from her home in Toronto.

"I think when you're trying to make a film it's such a struggle to get everything together, and get the financing, that you don't really believe it's going to happen.

"So to all of a sudden get these people in a room was actually a little bit of a shock."

Not that it all came together easily.

From the start Polley pictured Christie, Dukakis, and Gordon Pinsent in the main roles, but getting them to play those parts took some convincing.

"In the case of Julie it was hard," Polley said.

"I wrote the part for her, and I was friends with her, but I knew that it was going to be an uphill battle to get her - she's just not somebody who rushes into acting jobs.

"It took about eight months of phone calls, emails and listening to her concerns, and in the end she did it, which was great because I really couldn't have imagined anyone else playing the part."

The film is based on a short story by Alice Munro called The Bear Came Over the Mountain, about a man coming to terms with the institutionalisation of his Alzheimer's-affected wife, and how he copes when she transfers her affections to another man.

Polley fell in love with the story and wrote the screenplay herself.

"I think what really drew me to the short story was that it was incredibly romantic, but not at all in an idealistic way," she says.

"It was completely grounded in reality and all its complications and nightmares, but there's some kind of intangible thread that remains between these two people, despite how many times they may have betrayed each other, or felt abandoned by each other.

"That to me rang true, and it spoke to a kind of marriage that I think doesn't get that much air time."

Polley spent months researching Alzheimer's disease, talking to doctors and families who had dealt with it in order to present an accurate depiction of the condition.

"The thing is every Alzheimer's case is totally different," she says.

"So there are some people who feel like this is a moment by moment description of what they went through with their mother or their wife, but there are other people it feels completely wrong to because that wasn't their experience."

The film was selected for the Toronto and Sundance film festivals and has sparked rumours of an Oscar nomination for Christie.

The sensitive treatment of the subject, the subtlety of the script and the assuredness of the direction have not been missed by critics who have heaped praise on Polley, and named her a director to watch.

"I'm very flattered by it," says Polley, clearly uncomfortable with the hype.

"But in a way I felt like it wasn't a great mystery how to tell this story.

"So I'm happy people feel that way, but I sort of feel it's the film anybody would have made if they'd made a film of the story."

Toronto-based Polley says she has no intention to move to the US to further her career, and is happy living and working in Canada.

With its snow-covered scenery set to a Neil Young soundtrack, Away From Her is a noticeably Canadian film. But Polley says that wasn't a deliberate move.

"I didn't place a great emphasis on making sure that it felt Canadian, but I did put a big emphasis on making sure I wasn't avoiding it seeming Canadian," she said.

"I think there has been a really big push to make our films seem less and less Canadian for the last few years."

She says the Australian and Canadian film industries are struggling with the same issues in that respect.

"Australia and Canada have an enormous amount in common from what I can tell," Polley says.

"(Both) have very distinct cultural identity and yet feeling somewhat colonised - obviously historically by the English, and then culturally by the Americans.

"At first I think both Canada and Australia were famous for making more sort of artistic films, and then we both went through this phase of commercialisation where all our movies were for export, and then there was this real push to try to make our movies more American.

"It seems to me that we're both slowly edging our way back to what we're really good at."

Away From Her opens on October 4.

National Nine News

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Thursday, September 20, 2007

Amnesia in The New Yorker

From the current issue of The New Yorker:

The Abyss
Music and amnesia
by Oliver Sacks
September 24, 2007

The experience of Clive Wearing and his spouse, Deborah.


[ ... Read the article ... ]

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Wednesday, September 19, 2007

Neuropsychology Abstract of the Day: Aphasia

van de Sandt-Koenderman WM, Wiegers J, Wielaert SM, Duivenvoorden HJ, & Ribbers GM. A computerised communication aid in severe aphasia: An exploratory study. Disability and Rehabilitation. 2007 Apr 30;:1-9 [Epub ahead of print].

Rijndam Rehabilitation Center, Rotterdam.

Purpose. To investigate the efficacy of TouchSpeak (TS), a handheld computerised communication aid for aphasia. Method. A pre-post one-group design was used with a referred sample of 34 patients with a severe aphasia and a need for alternative and augmentative communication (AAC). The participants were trained to use TS in two self-chosen communicative situations. The ability to navigate the hierarchical vocabulary and overall communicative ability were assessed. Participants rated their communicative success with and without TS. Three years after completion of the training, participants were interviewed about their present use of TS. Results. In total, 76% used TS outside the clinic in two trained communicative situations. Overall communicative ability improved, as tested in untrained scenarios. Quality of communication with TS was rated higher than without TS. Fifty per cent obtained their own TS after the training and after 3 years 6% still used TS. Conclusions. Aphasic communication can be supported effectively by TS. Patients with a severe aphasia are able to master a hierarchical computerised vocabulary and to use it in daily life for specific communicative situations. In addition, TS may also have a generalised effect on overall communicative ability. For most patients, the supportive role of TS is temporary.

PMID: 17852317 [PubMed - as supplied by publisher]

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Friday, September 07, 2007

Starting Work on My New Book

This weekend I crack open the files on my next book and begin work on it, which I plan to complete by the end of 2008. This will be a weekend and vacation-time effort, which is the only way I can fit it in.

I've co-authored three academic books in the past and written a number of general-readership articles, but this will be my first venture into a book-length work written for a more general audience. The closest I've come to this in the past was a monograph (monograph:book as novella: novel) on magnetic resonance imaging (MRI) waaaay back in 1984, so I'm looking forward to the task!

The topic is on my area of expertise: the neuropsychological assessment of persons and what we can learn from these tests about the brain-behavior functioning of individuals.

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Thursday, September 06, 2007

Neuropsychology Abstract of the Day: Speech and the Cerebellum

Ackermann H, Mathiak K, & Riecker A. The contribution of the cerebellum to speech production and speech perception: Clinical and functional imaging data. Cerebellum. 2007; 6(3): 202-13.

Department of General Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen.

A classical tenet of clinical neurology proposes that cerebellar disorders may give rise to speech motor disorders (ataxic dysarthria), but spare perceptual and cognitive aspects of verbal communication. During the past two decades, however, a variety of higher-order deficits of speech production, e.g., more or less exclusive agrammatism, amnesic or transcortical motor aphasia, have been noted in patients with vascular cerebellar lesions, and transient mutism following resection of posterior fossa tumors in children may develop into similar constellations. Perfusion studies provided evidence for cerebello-cerebral diaschisis as a possible pathomechanism in these instances. Tight functional connectivity between the language-dominant frontal lobe and the contralateral cerebellar hemisphere represents a prerequisite of such long-distance effects. Recent functional imaging data point at a contribution of the right cerebellar hemisphere, concomitant with language-dominant dorsolateral and medial frontal areas, to the temporal organization of a prearticulatory verbal code ('inner speech'), in terms of the sequencing of syllable strings at a speaker's habitual speech rate. Besides motor control, this network also appears to be engaged in executive functions, e.g., subvocal rehearsal mechanisms of verbal working memory, and seems to be recruited during distinct speech perception tasks. Taken together, thus, a prearticulatory verbal code bound to reciprocal right cerebellar/left frontal interactions might represent a common platform for a variety of cerebellar engagements in cognitive functions. The distinct computational operation provided by cerebellar structures within this framework appears to be the concatenation of syllable strings into coarticulated sequences.

PMID: 17786816 [PubMed - in process]

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Wednesday, September 05, 2007

Neuropsychology Abstract of the Day: Cognitive Function in Pediatric Neuro-oncology

Nathan PC, Patel SK, Dilley K, Goldsby R, Harvey J, Jacobsen C, Kadan-Lottick N, McKinley K, Millham AK, Moore I, Okcu MF, Woodman CL, Brouwers P, Armstrong FD; Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer. Guidelines for identification of, advocacy for, and intervention in neurocognitive problems in survivors of childhood cancer: A report from the Children's Oncology Group. Archives of Pediatric and Adolescent Medicine. 2007 Aug; 161(8): 798-806.

Division of Haematology/Oncology, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada.

With modern therapies and supportive care, survival of childhood cancer has increased considerably. Patients who have survived cancers involving the central nervous system or who have received therapy toxic to the developing brain are at risk of long-term neurocognitive sequelae. Negative outcomes are observed most frequently in survivors of acute lymphoblastic leukemia and brain tumors. The Children's Oncology Group Long-term Follow-up Guidelines Task Force on Neurocognitive/Behavioral Complications After Childhood Cancer has generated risk-based, exposure-related guidelines designed to direct the follow-up care of survivors of pediatric malignancies based on a comprehensive literature review and expert opinion. This article expands on these guidelines by reviewing the risk factors for the development of neurocognitive sequelae and describing the expected pattern of these disabilities. We herein present recommendations for the screening and management of neurocognitive late effects and outline important areas of school and legal advocacy for survivors with disabilities. Finally, we list resources that can guide patients, their parents, and their medical caregivers as they face the long-term neurocognitive consequences of cancer therapy.
PMID: 17679663 [PubMed - indexed for MEDLINE]

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The Healthy Brain Initiative: Promoting Cognitive Health

The Healthy Brain Initiative website.

From the website:

[snip]

"The lack of cognitive health – from mild cognitive decline to dementia—can have profound implications for an individual’s health and well-being. Older adults and others experiencing cognitive decline may be unable to care for themselves or to conduct necessary activities of daily living, such as meal preparation and money management. Limitations in the ability to effectively manage medications and existing medical conditions are of particular concern when an individual is experiencing cognitive decline or dementia. If cognitive decline could be prevented or better treated, lives of many older adults could be improved.

"Opportunities for maintaining cognitive health are growing as public health professionals gain a better understanding of risk factors for cognitive decline. The public health community should embrace cognitive health as a priority, invest in its promotion, and enhance our ability to move scientific discoveries rapidly into public health practice."

[snip]

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Tuesday, September 04, 2007

Happy Third Anniversary to Me!

BrainBlog turns three years old today.

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Neuropsychology Abstract of the Day: Chronic Congestive Heart Failure and Neuropsychological Function

Vogels RL, Oosterman JM, van Harten B, Scheltens P, van der Flier WM, Schroeder-Tanka JM, & Weinstein HC. Profile of Cognitive Impairment in Chronic Heart Failure. Journal of the American Geriatrics Society. 2007 Aug 28; [Epub ahead of print].

Department of Neurology, Sint Lucas-Andreas Hospital, Amsterdam, The Netherlands.

OBJECTIVES: To determine the frequency and pattern of cognitive dysfunction in outpatients with chronic congestive heart failure (CHF) and to identify the corresponding demographic and clinical correlates. DESIGN: Case-control study. SETTING: Outpatient clinic in a community hospital. PARTICIPANTS: Sixty-two outpatients with CHF, 53 controls diagnosed with cardiovascular disease uncomplicated by CHF (cardiac controls), and 42 healthy controls were investigated. MEASUREMENTS: Neuropsychological assessment included tests of mental speed, executive function, memory, language, and visuospatial function. Composite z-scores for five cognitive domains and mean z-score for overall cognitive performance were computed. The cutoff score to indicate cognitive impairment was defined as the overall healthy participants' cognitive z-score minus 2 standard deviations. Independent demographic and clinical predictors of cognitive impairment were identified using linear regression analysis. RESULTS: Patients with CHF showed a pattern of general cognitive impairment, including impairment of executive function, memory, language, mental speed, and attention. Twenty-five percent (P=.04) of patients with CHF were classified as cognitively impaired, compared with 15% of the cardiac controls and 4% of the healthy controls. Independent predictors of cognitive impairment in patients with CHF were estimated intelligence, New York Heart Association class, and presence of the apolipoprotein (Apo)E epsilon4 allele. CONCLUSION: Cognitive dysfunction is relatively common in patients with CHF, with deficits being most prominent in the domains of executive function, memory, language, and mental speed. Disease severity and ApoE genotype are likely to be important determinants for cognitive impairment in patients with chronic CHF.

PMID: 17727641 [PubMed - as supplied by publisher]

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Sunday, September 02, 2007

Promoting Academic Writing

Interesting piece in today's New York Times about writers taking promotional book "tours" via blogs:

The Author Will Take Q.’s Now
By KARA JESELLA
Published: September 2, 2007

[snip]

Bloggers have written about books since, well, the beginning of blogging. But a blog book tour usually requires an author or publicist to take the initiative, reaching out to bloggers as if they were booksellers and asking them to be the host for a writer’s online visit. Sometimes bloggers invite authors on their own. In an age of budget-conscious publishers and readers who are as likely to discover books from a Google search as from browsing at a bookstore, the blog book tour makes sense. Although a few high-profile authors have had their books sent to bloggers — James Patterson recently promoted a young-adult book this way — most of the authors are lesser-known and less likely to be reviewed in the mainstream press.

[snip]

[ Read the full article ... ]

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Chemotherapy and Neuropsychological Functioning

From yesterday's Milwaukee Journal-Sentinel:

Lost in cancer's fog
'Chemobrain' impairs thinking, memory after chemotherapy; anecdotal brain effects are just starting to get serious study

By JOHN FAUBER
01 September 2007
Milwaukee Journal-Sentinel

[snip]

In two small groups of testicular and breast cancer patients, between 60% and 70% of the patients experienced some cognitive decline that was tied to the onset of their chemotherapy, said Christina Meyers, a professor and chief of neuropsychology at the M.D. Anderson Cancer Center in Houston.

"It's subtle," she said. "We are not talking about dementia or anything grossly obvious."

Within one year, about half of the patients were back to their pretreatment levels of cognitive ability, Meyers said.

[snip]

[ ... Read the full article ... ]

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