Source: http://www.thehollywoodgossip.com/2013/04/jesus-franco-dies-horror-film-legend-was-82/
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Friday, April 5, 2013
Phase 1 ALS trial is first to test antisense treatment of neurodegenerative disease: No serious adverse effects reported
Apr. 3, 2013 ? The initial clinical trial of a novel approach to treating amyotrophic lateral sclerosis (ALS) -- blocking production of a mutant protein that causes an inherited form of the progressive neurodegererative disease -- may be a first step towards a new era in the treatment of such disorders. Investigators from Massachusetts General Hospital (MGH) and Washington University School of Medicine report that infusion of an antisense oligonucleotide against SOD1, the first gene to be associated with familial ALS, had no serious adverse effects and the drug was successfully distributed thoughout the central nervous system.
"This therapy directly targets the cause of this form of ALS -- a mutation in SOD1, which was originally discovered here at the MGH by my mentor Robert Brown," says Merit Cudkowicz, MD, chief of Neurology at MGH and senior author of the report in Lancet Neurology, which has been released online. "It's very exciting that we have reached a stage when we can start clinical trials against this type of ALS."
ALS causes the death of motor neurons in the brain and spinal cord, stopping transmission of neural signals to nerve fibers and leading to weakness, paralysis and usually death from respiratory failure. Only 10 percent of ALS cases are inherited, and mutations in SOD1 -- which produce an aberrant, toxic form of the protein -- account for about 20 percent of familial cases. Although that first SOD1 mutation was identified 20 years ago by the team lead by Brown -- who is now professor and chief of Neurology at the University of Massachusetts Medical School -- a technology that directly addresses such mutations became available only recently.
The current study, the first author of which is Timothy Miller, MD, PhD, of Washington University, used what are called antisense oligonucleotides -- small, single-stranded DNA or RNA molecules that prevent production of a protein by binding to its messenger RNA. While antisense medications have been tested against several types of disease, this was the first trial in a neurological disorder, making the assurance of safety -- a primary goal of a phase 1 study -- particular important. Studies in animal models led by Miller and others found that the experimental antisense drug used in this trial reduced expression of mutated and nonmutated SOD1 and slowed the progression of ALS.
Conducted at the MGH, Washington University, Johns Hopkins University and the Methodist Neurological Institute in Houston, the trial enrolled a total of 21 patients with SOD1 familial ALS. Four sequential groups of participants received spinal infusions over an 11-hour period of the antisense drug or a placebo, with the active drug being administered at one of four dosage levels. Since participants in one group were free to join a subsequent group more than 60 days later, seven received two infusions and two received a total of three.
Some of the participants reported the type of adverse effects typically associated with spinal infusions -- headache and back pain -- with no difference between the active drug and placebo groups. Participants who receive subsequent infusions reported fewer adverse effects. Cerebrospinal fluid samples taken immediately after infusion revealed the presence of the antisense oligonucleotidein all participants receiving the drug at levels close to what was predicted based on animal studies. Analysis of spinal cord samples from one participant who had later died from ALS found drug levels highest at the site of the infusion and lowest at the furthest point and suggested that prior estimates of how long the drug would persist in the spinal cord were accurate.
Cudkowicz notes that the next step will be a larger study to address long-term safety and take a first look at the effectiveness of antisense treatment against ALS "This is a very important step forward for neurodegenerative disorders in general," she explains. "There are other ALS gene mutations that antisense technology may be useful against. There also is an ongoing study of a different oligonucleotide against spinal muscular atrophy, and ongoing preclinical studies in Huntington's disease, myotonic dystrophy and other neurological disorders are in development.
"The first person with ALS that I cared for had SOD1 ALS," she adds, "and I promised her a commitment to finding a treatment for this form of the disease. It's so gratifying to finally be at the stage of knowledge where we can start testing this treatment in patients with SOD1 ALS. We also hope that this treatment may apply to the broader population of patient with sporadic ALS." Cudkowicz is the Julieanne Dorn Professor of Neurology at Harvard Medical School.
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The above story is reprinted from materials provided by Massachusetts General Hospital.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- Timothy M Miller, Alan Pestronk, William David, Jeffrey Rothstein, Ericka Simpson, Stanley H Appel, Patricia L Andres, Katy Mahoney, Peggy Allred, Katie Alexander, Lyle W Ostrow, David Schoenfeld, Eric A Macklin, Daniel A Norris, Georgios Manousakis, Matthew Crisp, Richard Smith, C Frank Bennett, Kathie M Bishop, Merit E Cudkowicz. An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: a phase 1, randomised, first-in-man study. The Lancet Neurology, 2013; DOI: 10.1016/S1474-4422(13)70061-9
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/pNA1_xAHlrM/130403141451.htm
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Thursday, April 4, 2013
Immigration bill envisions new farm worker program
WASHINGTON (AP) ? Sweeping immigration legislation taking shape in the Senate will aim to overhaul the nation's agriculture worker program to create a steady supply of labor for farmers and growers, who rely more than any other industry on workers who have come to the country illegally.
Farm workers already here would get a speedier path to legal status than other immigrants in the country illegally, and a likely new visa program would make it easier for foreign workers to come to the U.S. Policymakers aim to install such workers in place of the half or more of the nation's farm labor workforce estimated to be in the country illegally.
Negotiators have been working to finalize an agreement in time for the measure to be included in bipartisan legislation expected to be released next week, but disagreements on wages and numbers of visas are proving tough to solve.
Labor groups are accusing growers of pushing to lower farmworkers' wages, while growers dispute that and say they want to pay a fair wage. Meanwhile, labor is resisting growers' attempts to increase the potential numbers of new workers who would come in, as growers argue their industry's viability depends on a strong new labor supply.
"It comes down to either we're importing our labor or we're importing our food, and if we don't have access to a legal supply of labor we will start going offshore," said Kristi Boswell, director of congressional relations for the American Farm Bureau Federation.
The issue has gotten little public attention in an immigration debate focused on securing the border, creating a path to citizenship for the 11 million immigrants living in the country illegally, and designing a new visa program for low-skilled workers outside of agriculture. But for states from California to Georgia to Florida with booming agriculture industries, it's a critical part of the puzzle.
At least 50 percent and as much as 70 or 80 percent of the nation's farm workers arrived illegally, according to labor and industry estimates. Growers say they need a better way to hire labor legally, and advocates say workers can be exploited and need better protections and a way to earn permanent residence.
"One thing that we know is that there's not an industry that will benefit more from a new immigration program than agriculture," said Giev Kashkooli, United Farm Workers vice president. "The problem is industry needs people who are both willing and able to do the work. And it's difficult work."
The reason agriculture uses so much illegal labor has to do with the need for workers, but also the inadequacy of current immigration programs. There is a 10-month visa program for farm workers, called the H2A visa, but growers argue it's so hard to use that once they've completed the paperwork whatever crop they needed picked may well have withered.
There were about 55,000 H2A visas issued in 2011, representing a small percentage of the nation's approximately 2 million farm workers.
Part of the solution, growers and unions say, is to create a more permanent agricultural workforce. Senators would likely accomplish this by giving a new "blue card" visa granting legal status to farm workers who've worked in the industry for at least two years and intend to remain in it for at least five years more.
At that point, potentially, these workers could become eligible for green cards, which allow permanent residency and eventual citizenship ? faster than the 10-year path to a green card that other immigrants in the country illegally are expected to face under the Senate immigration bill.
Separately, growers are pushing to replace the H2A visa program with an entirely new program with visas offering multiyear stays. But there is disagreement over how many such visas would be offered and how much money workers would make ? the same issues that hung up a deal between the U.S. Chamber of Commerce and the AFL-CIO over nonagricultural low-skilled workers before a resolution was reached over the weekend.
The UFW contends that growers are trying to push farm workers below their current average wage of $10.80 an hour, but growers say that wage is skewed by a small number of high earners and that most farm workers make less. In light of the dispute, the UFW has begun to argue that a new visa program may not be necessary at all.
The two-pronged structure of the emerging deal is similar to legislation called AgJobs negotiated in years past that never became law. Because of that history, the agriculture issue is being handled differently from other parts of the Senate immigration bill. It's being negotiated by four senators ? Dianne Feinstein, D-Calif., Orrin Hatch, R-Utah, Marco Rubio, R-Fla., and Michael Bennet, D-Colo. ? only two of whom, Rubio and Bennet, are part of the so-called Gang of Eight senators writing the overall bill.
All involved hope for a resolution of an issue that has been in need of one for years, ever since the last major immigration overhaul, in 1986, failed to establish a workable visa program for farmworkers and others.
"We made our bed and have been lying in it ever since so this is a chance to get it right and not repeat those failures," said Craig J. Regelbrugge, co-chair of the Agriculture Coalition for Immigration Reform.
___
Follow Erica Werner on Twitter: https://twitter.com/ericawerner
Source: http://news.yahoo.com/immigration-bill-envisions-farm-worker-program-070531010--finance.html
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Wednesday, April 3, 2013
IRS weighs changes to Obama healthcare investment tax rules
By Kim Dixon
WASHINGTON (Reuters) - Businesses and wealthy owners of estates and trusts asked the IRS on Tuesday for changes to a part of President Barack Obama's 2010 healthcare law that has received comparatively little attention: a 3.8 percent tax on investment income intended to provide the bulk of the law's funding.
The tax kicks in this year, with U.S. taxpayers accounting for it for the first time in their tax returns for 2013. It is projected to raise more than $100 billion over a decade to help pay for health insurance for millions of Americans who lack it.
The Internal Revenue Service in December issued proposed regulations to implement the tax. On Tuesday, lawyers for various small and big businesses and owners of estates and trusts urged the agency during a public hearing over the IRS's proposed rules to clarify gray areas before they become final.
The tax applies to the investment income of individual taxpayers earning more than $200,000 a year, or households with income above $250,000. It is applied on top of the 20 percent tax now on investment income from dividends and capital gains.
Murky areas in the proposed IRS rules involve rental income earned by individual or businesses and income paid out by trusts, according to witnesses who testified at the hearing.
Michael Grace, an attorney at law firm Whiteford Taylor & Preston, represents mostly small- and medium-sized businesses that do business as "pass-through" entities, such as limited liability corporations, partnerships and S-corporations.
In these businesses, profits are not retained by the business or distributed to public shareholders, but passed through to the partners, who are then taxed on that income. These entities will potentially be subject to the new tax.
Grace said conflicting tax code definitions of investment income make it difficult to determine if, for example, an auto rental company or real estate developer would be subject to the tax.
"You start with the premise that rents are generally subject to the tax, but there are all these different ways you legally can escape it," Grace said. "People are confused."
Grace urged IRS officials to spell out in final regulations how to determine whether rents under various scenarios are subject to the 3.8 percent tax.
The net investment tax applies to business income considered passive under current tax rules. Income is considered passive if it comes from "rental activity" or if the individual does not "materially participate" in running the business, generally defined as spending more than 500 hours a year in the activity.
The National Business Aviation Association, which represents individuals and companies that use their own aircraft or manage it for other companies, also proposed changes.
John Hoover, an attorney representing the group, said rules are unclear regarding how companies lease business jets and other aircraft to related entities and how their income is treated.
"We have this question - what do you look at to evaluate whether you have an ordinary and necessary activity?" he said.
(Editing by Kevin Drawbaugh; and Will Dunham)
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New genetic evidence suggests a continuum among neurodevelopmental and psychiatric disorders
Apr. 2, 2013 ? A paper published this month in the medical journal The Lancet Neurology suggests that a broad spectrum of developmental and psychiatric disorders, ranging from autism and intellectual disability to schizophrenia, should be conceptualized as different manifestations of a common underlying denominator, "developmental brain dysfunction," rather than completely independent conditions with distinct causes.
In "Developmental Brain Dysfunction: Revival and Expansion of Old Concepts Based on New Genetic Evidence," the authors make two key points:
? Developmental disorders (such as autism and intellectual disability) and psychiatric disorders (such as schizophrenia and bipolar disorder), while considered clinically distinct, actually share many of the same underlying genetic causes. This is an example of "variable expressivity:" the same genetic variant results in different clinical signs and symptoms in different individuals. ? When quantitative measures of neuropsychological and neurobehavioral traits are studied instead of categorical diagnoses (which are either present or absent) and individuals are compared to their unaffected family members, it is possible to more accurately demonstrate the impact of genetic variants.
According to Andres Moreno De Luca, M.D., research scientist at the Autism and Developmental Medicine Institute at Geisinger Health System and article co-author, "Recent genetic studies conducted in thousands of individuals have shown that identical genetic mutations are shared among neurodevelopmental disorders that are thought to be clinically distinct. What we have seen over the past few years is that genetic mutations that were initially found in individuals with one disorder, such as intellectual disability or autism, are then identified in people with an apparently different condition like schizophrenia, epilepsy, or bipolar disorder."
"It turns out that the genes don't respect our diagnostic classification boundaries, but that really isn't surprising given the overlapping symptoms and frequent co-existence of neurodevelopmental disorders," said Scott M. Myers, M.D., autism specialist at Geisinger Health System and article co-author.
"We believe this study supports use of the term 'developmental brain dysfunction' or DBD, which would encompass the broad spectrum of neurodevelopmental and neuropsychiatric disorders," said David H. Ledbetter, Ph.D., executive vice president and chief scientific officer at Geisinger Health System, and article co-author. "Additionally, it is clear that diagnostic tools such as whole genome analysis for both children and their families are essential when diagnosing and treating these disorders in order to ensure the most personalized treatment."
An example used in the study was analysis of intelligence quotient (IQ) scores. The average IQ score in the general population is 100. Historically, the medical community has defined intellectual disability as an IQ of less than 70 (with concurrent deficits in adaptive functioning). But according to Dr. Ledbetter, there is little difference in the function of a child with an IQ of 69 versus 71, yet one may be diagnosed with a disability and the other may not.
"We know a variety of factors contribute to IQ score, including genetics, as a child's IQ is highly correlated with that of his or her parents and siblings. Therefore, an important factor to take into consideration when interpreting IQ is family background," said Dr. Ledbetter. "Imagine if we have a child with a genetic abnormality, but the child's IQ is 85. Technically, we would not diagnose this child with a disability. However, if the family of this child has IQs around 130, we could consider that this child's genetic anomaly has 'cost' him or her 45 IQ points -- a very substantial difference."
According to Dr. Myers, "One implication of this concept is that studies designed to investigate the causes and mechanisms of developmental brain dysfunction should focus on measurement of quantifiable neuropsychological and neurobehavioral traits across groups of individuals with different clinical diagnoses. Another is that whenever possible, individuals with a particular genetic variant or other risk factor should be compared to their unaffected family members, not just to population norms."
Other authors on the paper were Thomas Challman, M.D. of Geisinger; Daniel Moreno De Luca, M.D., of Yale University, New Haven, Conn.; and David Evans, Ph.D., of Bucknell University, Lewisburg, Pa.
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The above story is reprinted from materials provided by Geisinger Health System, via Newswise.
Note: Materials may be edited for content and length. For further information, please contact the source cited above.
Journal Reference:
- Andres Moreno-De-Luca, Scott M Myers, Thomas D Challman, Daniel Moreno-De-Luca, David W Evans, David H Ledbetter. Developmental brain dysfunction: revival and expansion of old concepts based on new genetic evidence. The Lancet Neurology, 2013; 12 (4): 406 DOI: 10.1016/S1474-4422(13)70011-5
Note: If no author is given, the source is cited instead.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.
Source: http://feeds.sciencedaily.com/~r/sciencedaily/~3/p_nM1XEl6xs/130402182454.htm
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Diversification in ancient tadpole shrimps challenges the term 'living fossil'
Apr. 2, 2013 ? The term 'living fossil' has a controversial history. For decades, scientists have argued about its usefulness as it appears to suggest that some organisms have stopped evolving. New research has now investigated the origin of tadpole shrimps, a group commonly regarded as 'living fossils' which includes the familiar Triops. The research reveals that living species of tadpole shrimp are much younger than the fossils they so much resemble, calling into question the term 'living fossil'.
Darwin informally introduced the term 'living fossil' in On the Origin of Species when talking about the platypus and lungfish, groups that appear to have diversified little and appear not to have changed over millions of years. For him living fossils were odd remnants of formerly more diverse groups, and suggestive of a connection between different extant groups. Ever since, the term has been widely used to describe organisms such as the coelacanth, the horseshoe crab and the ginkgo tree. The term has been controversial, as it appears to suggest that evolution has stopped altogether for these organisms, and some scientists have argued that it should be abandoned.
Tadpole shrimps are a small group of ancient crustaceans (a group which includes the familiar Triops) that are often called 'living fossils', because the living species look virtually identical to fossils older than the dinosaurs. Analysing DNA sequences of all known tadpole shrimps, and using fossils from related crustacean groups -- such as the water flea and the brine shrimp -- the team of researchers, from the University of Hull, University of Leicester and the Natural History Museum in London, showed that tadpole shrimps have in fact undergone several periods of radiation and extinction. The new study is published today in PeerJ, a new peer reviewed open access journal in which all articles are freely available to everyone (https://PeerJ.com).
Different species of tadpole shrimp often look very similar (they are called 'cryptic species'), and so it is only with the advent of DNA sequencing that scientists have realized that they are a surprisingly diverse group. The team's results uncovered a total of 38 species, many of them still undescribed. This abundance of 'cryptic species' makes it very difficult for fossils to be assigned to any particular species as they all look remarkably similar. For example, 250-million-year-old fossils have been assigned to the living European species Triops cancriformis whereas the team's results indicate that the living T. cancriformis evolved less than 25 million years ago. First author Tom Mathers says "In groups like tadpole shrimps where cryptic speciation is common, the fossil record says very little about patterns of evolution and diversification and so the term 'living fossil' can be quite misleading. For this reason, we used fossils from related groups to gain an understanding about the evolution of tadpole shrimps."
The lead author Africa G?mez said, "Living fossils evolve like any other organism, they just happen to have a good body plan that has survived the test of time. A good analogy could be made with cars. For example the Mini has an old design that is still selling, but newly made Minis have electronic windows, GPS and airbags: in that sense, they are still 'evolving', they are not unchanged but most of the change has been 'under the hood' rather than external. By comparison, organisms labeled as 'living fossils' such as tadpole shrimps, are constantly fine-tuning their adaptation to their environment. Although outwardly they look very similar to tadpole shrimp fossils from the age of the dinosaurs, their DNA and reproductive strategies are relatively hidden features that are constantly evolving. The flexibility of their reproductive strategies, which our research has revealed, could be the evolutionary trick that has allowed them to persist as a morphologically conservative group for so long."
Background
Tadpole shrimps include the familiar Triops -- which is often sold as dried eggs in toy shops -- that can easily be grown at home. Their fossils can be found from the Carboniferous, 300 million years ago, and the group has survived several mass extinction events. Currently, tadpole shrimps occupy a range of temporal aquatic habitats with different water chemistry conditions, such as hypersaline Australian lakes, rice fields, coastal pools, river floodplains and arctic ponds. Their eggs can survive in a dry state for several decades, only hatching when suitable conditions return.
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The above story is reprinted from materials provided by PeerJ.
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Journal Reference:
- Thomas C. Mathers, Robert L. Hammond, Ronald A. Jenner, Bernd H?nfling, Africa G?mez. Multiple global radiations in tadpole shrimps challenge the concept of ?living fossils?. PeerJ, 2013; 1: e62 DOI: 10.7717/peerj.62
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Disclaimer: Views expressed in this article do not necessarily reflect those of ScienceDaily or its staff.
Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/E7oZsAI-y4Q/130402091641.htm
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Michael Jackson Wrongful Death Case: Jury Selection Begins
LOS ANGELES ? Jury selection began Tuesday in a lawsuit filed by Michael Jackson's mother against the promoter of the late pop star's planned comeback concerts.
Dozens of prospective jurors answered written questionnaires that gauged their ability to serve on the trial, which may last three months. One 24-page section of the questionnaire focused on each person's knowledge and opinions on Jackson's life, his music, his family, as well as media coverage and whether they would have a problem deciding a multimillion-dollar case.
Katherine Jackson's case accuses concert giant AEG Live of failing to properly investigate the former doctor who was convicted of involuntary manslaughter for the superstar's June 2009 death.
AEG has denied wrongdoing and its attorney, Marvin Putnam, has said the company could not have foreseen circumstances that led to Jackson dying from an overdose of the powerful anesthetic propofol.
The trial will revisit the singer's final days, as well as his struggles with insomnia and prescription drugs.
Jackson's family is seeking $40 billion, but jurors will determine any damage amounts awarded. If they award damages, jurors will have to determine how much responsibility AEG Live has for Jackson's death.
The panel also could determine that the pop superstar was responsible for his own demise and limit the amount his family can collect.
The court proceedings, though routine, drew interest from fans and media outlets, who parked satellite trucks and cameras outside the courthouse. Katherine Jackson, who sued AEG in 2010 and has had her case trimmed to a single allegation of negligent hiring and supervision, did not attend the first day of jury selection.
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