Removal of fibroids that distort the womb cavity may prevent recurrent miscarriages

 by Biomechanism 

Researchers have found for the first time, a firm evidence that fibroids are associated with recurrent miscarriages. They have also discovered that if they removed the fibroids that distorted the inside of the womb, the risk of miscarriage in the second trimester of pregnancy was reduced dramatically – to zero.

"It has been recognised since the 1980s that women with unexplained recurrent miscarriage have very good pregnancy outcomes following referral to a dedicated clinic without the need for any intervention, and with psychological supportive care, i.e. tender loving care, alone.

The study, which is published online in Europe’s leading reproductive medicine journal Human Reproduction [1] on Wednesday, is the culmination of 20 years of investigation into recurrent miscarriage by Professor Tin-Chiu Li and his team at the recurrent miscarriage clinic at the University of Sheffield and Sheffield Teaching Hospitals (Sheffield, UK). In addition, for the first time it has given a reliable estimate of the prevalence of fibroids in women who have recurrent miscarriages.

Fibroids in or around the womb (uterus) are benign tumours composed of muscle and fibrous tissue. Although they have been associated with spontaneous miscarriage, until now there has been no evidence of their role in recurrent miscarriages (RM). The prevalence of fibroids has been estimated to be between 3-10% in women of reproductive age, but the prevalence is unknown in women who experience RM, which is defined as three or more consecutive miscarriages.

The researchers analysed data from 966 women who attended the Sheffield RM clinic. The women were scanned for uterine anomalies, including fibroids, via transvaginal ultrasound and radiology, and 79 were found to have fibroids. “This enabled us to calculate that the prevalence of fibroids was 8.2% among women with recurrent miscarriages; this has never been accurately reported before,” said one of the researchers, Dr Sotirios Saravelos, who is a clinical research Fellow at the University of Sheffield.

Fibroids were diagnosed and grouped into three classifications:

• Submucosal – these grow in the muscle beneath the inner lining of the womb wall and grow into the middle of the womb, distorting the cavity
• Intramural – these develop in the muscle wall of the womb and are the most common type of fibroid. They do not distort the cavity and have less than 50% protrusion into the serosal surface – the outer membrane lining the womb
• Subserosal – these grow outside the wall of the womb into the pelvis, do not distort the womb cavity, and have a greater than 50% protrusion out of the serosal surface.

Prof Li used minimally invasive surgery (hysteroscopy) to remove cavity-distorting (submucosal) fibroids from 25 women; 54 women with fibroids that did not distort the cavity had no surgery and they were matched with a control group of 285 women whose recurrent miscarriages were still unexplained after all investigations found nothing abnormal; these women also had no intervention.

In the 25 women who had undergone surgery, miscarriage rates in subsequent pregnancies during the second trimester fell from 21.7% to 0%. This translated to an increase in the live birth rate from 23.3% to 52%.

Dr Saravelos said: “This is the first time that it has been shown that removing fibroids that distort the uterine cavity may increase the chances of a subsequent live birth in women with recurrent miscarriages.”

The 54 women with fibroids not distorting the uterine cavity and who had had no surgery also did better after referral to the RM clinic. Pre-referral, the miscarriage rate during the second trimester was 17.6% and this fell to 0% after referral. Live birth rates went up from 20.6% to 70.4% in subsequent pregnancies. This was similar to results from the 285 women with unexplained RM; the second trimester miscarriage rate was 8% pre-referral to the clinic, falling to 1.8% post-referral, while live birth rates increased from 20.6% to 71.9% after referral.

Dr Saravelos said: “These results are interesting because they suggest that the finding of fibroids in women with recurrent miscarriage does not necessarily imply that the fibroids are the only cause of the miscarriage. In addition, they suggest that surgical intervention is not the only means whereby patients with recurrent miscarriage benefit from attending a specialised, dedicated clinic. However, for women with fibroids that distort the uterine cavity, our work shows that removing the fibroids can eliminate miscarriage during the second trimester and double the live birth rate in subsequent pregnancies.

“It has been recognised since the 1980s that women with unexplained recurrent miscarriage have very good pregnancy outcomes following referral to a dedicated clinic without the need for any intervention, and with psychological supportive care, i.e. tender loving care, alone. This usually takes the form of regular visits to a dedicated recurrent miscarriage clinic, regular antenatal scans to check the condition of the baby, reassurance to the mother from the specialist that everything is progressing well and specialist antenatal counselling throughout the pregnancy.

“Interestingly, although women may increase their live birth rate by up to 50% after psychological supportive care, the exact underlying mechanisms involved in this process are not entirely understood. In the present study, the fact that women with fibroids not distorting the uterine cavity do so well, suggests that they also do not have an underlying cause for recurrent miscarriage. As a result, they can also be considered as having ‘unexplained recurrent miscarriage’, and should be counselled that they have very good chances of a successful pregnancy without the need for any intervention or surgery and with the psychological supportive care offered by a dedicated recurrent miscarriage clinic.”

The main limitation of the study is that there was no control group for the women who had their fibroids removed and so it is not possible to tell whether they would have done better without surgery, after referral to the RM clinic. The researchers say that their work highlights the need to perform a randomised controlled trial to investigate this.

“The definitive study requires the recruitment of a rather large number of patients to be randomised between intervention and no intervention. This would require the input of several clinics in a multi-centre randomised controlled trial and its success would depend on the support of all clinics along with that of Sheffield,” said Dr Saravelos.

-Health News For Women in Pregnancy

____________

[1] “The prevalence and impact of fibroids and their treatment on the outcome of pregnancy in women with recurrent miscarriage”, by Sotirios H. Saravelos, Junhao Yan, Hassan Rehmani, and Tin-Chiu Li. Human Reproduction journal. doi:10.1093/humrep/der293

How Normal Cells Become Brain Cancers

 by Biomechanism 

Brain tumor specimens taken from neurosurgery cases at the University of California, San Francisco (UCSF) Medical Center has given scientists a new window on the transformation that occurs as healthy brain cells begin to form tumors.

The work may help identify new drugs to target oligodendroglioma, a common type of brain tumor, at its earliest stage, when it is generally most treatable. Any potential drugs identified will have to prove safe and effective in clinical trials, a process that can take several years.

Representative NG2+ cell pairs from tumor and non-neoplastic tissue stained for NG2 and EGFR. Scale bars represent 10 μM. Photo: Jason Bardi

As described in the journal Cancer Cell this month, the UCSF team found that the pool of cells from which oligodendroglioma tumors emerge normally divide “asymmetrically” by splitting into two unequal parts – like giving birth to fraternal twins who look different and have distinct fates. When these normal cells transform into cancer cells, they switch gears and begin dividing symmetrically, essentially giving birth to identical twins instead.

“This happens early – before the tumor forms, and it may provide a point to intervene in the process of tumor initiation,” said Claudia Petritsch, PhD, an assistant professor with the UCSF Brain Tumor Research Center who led the research.

The Brain Tumor Research Center is part of the UCSF Department of Neurological Surgery, which is consistently ranked by U.S. News & World Report as one of the top departments in the world. Its doctors perform more than 1,100 neurosurgeries a year to remove brain tumors, and in the last 30 years, this work has helped to build one of the most extensive brain tumor repositories in the United States, with tissue samples collected from more than 7,800 cases of cancer.

In their research, Petritsch and her colleagues used genetically engineered mice to identify that a protein called NG2 controls this switch, and they are working on ways to target genes that regulate the process as a way of fighting oligodendroglioma and perhaps other brain tumors.

Why Divisions Matter to Cancer

Oligodendrogliomas are unusual among brain tumors because they often respond to chemotherapy drugs. However, the tumor frequently returns in a form that is resistant to chemotherapy and requires repeated surgical removal.

Petritsch and her colleagues first discovered last year that oligodendroglioma tumors derive from a type of progenitor cell called “oligodendrocyte progenitors” that proliferate in the brain throughout life. These progenitors may also play an important role when the brain is injured by multiplying rapidly and helping heal wounds.

The new studies in mice suggest that lacking an injury, these progenitors divide mostly asymmetrically, maintaining an equilibrium of these cells within the brain. Progenitors can also switch gears and divide symmetrically instead. Scientists believe that allows the brain to provide an expanded pool of cells when needed.

Using mouse models of the tumors as well as tissue samples taken from people with the disease, Petritsch and her colleagues showed that before the tumors arise, the cells preemptively make this switch, transforming from dividing asymmetrically to dividing symmetrically.

They used bioinformatics to discover that dozens of regulators of asymmetric cell division including NG2 are dysregulated in oligodendrogliomas. The Petritsch lab calls these “asymmetry proteins” and argues that if mutated they probably cause the switch to abnormal cell divisions and thereby initiate the genesis of tumors. Modulating NG2 and dysregulated asymmetry proteins pharmacologically may restore normal division modes and provide a new way to fight the cancer with drugs.

The article, Asymmetry-Defective Oligodendrocyte Progenitors Are Glioma Precursors” by Sista Sugiarto, Anders I. Persson, Elena Gonzalez Munoz, Markus Waldhuber, Chrystelle Lamagna, Noemi Andor, Patrizia Hanecker, Jennifer Ayers-Ringler, Joanna Phillips, Jason Siu, Daniel Lim, Scott Vandenberg, William Stallcup, Mitchel S. Berger, Gabriele Bergers, William A. Weiss, and Claudia Petritsch appears in the September 13, 2011 issue of the journal Cancer Cell.

This work is supported by grants from the National Brain Tumor Foundation, the American Cancer Society, the American Brain Tumor Association, the National Cancer Institute, the UCSF Brain Tumor SPORE, the Brain Tumor Research Sobrato Fund, the Farber A and J Foundation, the Grove Foundation, the Samuel Waxman Cancer Research Foundation, the UCSF Sandler Program in Basic Science, the Swedish Society for Medical Research and Medical Research Council, and the Swiss National Science Foundation.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

AN ENTREPRENEUR’S ACHILLES HEEL: TIME MANAGEMENT

Entrepreneurs are often also visionaries. Yet if their time is consumed by juggling the many responsibilites it takes to keep their business going, they can lose the time it takes to step away and think up innovative ideas. According to Richard Branson, every CEO needs to step away and “look at the big picture.”

Richard Branson on Time Management

Editor’s Note: Entrepreneur Richard Branson regularly shares his business experience and advice with readers. What follows is the latest edited round of insightful responses. Ask him a question and your query might be the inspiration for a future column.

Q: Virgin is a large company with many diversified businesses and a culture of delegating. How do you avoid breakdowns in communication and ensure that good decisions are made? – Shezad Virji, Kenya

Q: How do you deal with the hundreds of emails you receive from readers? I know you are very busy. Do you have any secret? – Harvey Chen, China

A: Reading through recent emails, I was struck by the number of questions from readers about how entrepreneurs can better manage their own time as they manage their complexbusinesses.

As a successful business matures and expands, bureaucracy usually starts to take hold and members of the senior management team find themselves overwhelmed by the sheer number of meetings and volume of correspondence. At this stage, an entrepreneur faces the challenge of how to effectively manage this new structure — a transition that has been the undoing of many enterprises.

First, let’s look at how to manage your own time. I receive 300 to 400 messages a day, so time management is an issue for me. I’m aware some senior executives simply delete all emails from people they don’t know personally, arguing that most of the messages just create distraction. To them, it is not worth the effort of weeding through the emails to find those that contain useful information. But I find this approach impolite and bad for business.

Recalling a time when I was just starting out and needed advice, I try to respond to as many reader emails as I can. I read through the list every morning and dictate quick answers to my assistants, pass some to colleagues, and usually write a couple of longer, more detailed responses myself. This is the most effective way of dealing with my inbox, and while doing so, I learn about trends that may affect Virgin businesses or about problems that need my attention.

You must manage your Blackberry; do not let it manage you. Many executives check their smartphones throughout meetings and during off-hours. This is not good for concentration, and has a negative impact on decision making. Use it only in bursts: check emails for an hour or so and then put it away so you can focus on the task at hand.

Shirdi Sai Baba bhajans ~ THE NEHRU CENTRE ~ LOndon Pt 2 - YouTube.FLV

Scientists Reveal Molecular Sculptor of Memories

Artist's rendering of neurons. (Credit: © Sebastian Kaulitzki / Fotolia)

ScienceDaily  — Researchers working with adult mice have discovered that learning and memory were profoundly affected when they altered the amounts of a certain protein in specific parts of the mammals' brains.

The protein, called kibra, was linked in previous studies in humans to memory and protection against late-onset Alzheimer's disease. The new work in mice, reported in the Sept. 22 issue of Neuron, shows that kibra is an essential part of a complex of proteins that control the sculpting of brain circuitry, a process that encodes memory.

"There are populations of humans who are slightly smarter and have better memory recall than others, and these traits have been mapped to the gene that codes for the kibra protein" says Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator. "Our studies in mice show that this same gene is involved in the operation of synapses, through which neurons communicate, and in brain plasticity, suggesting that's what its role might be in humans too."

In their lab, Huganir and neuroscience graduate student Lauren Makuch isolated kibra from mouse brain cells and confirmed by standard biochemical tests that it interacted with a neurotransmitter receptor in the brain known as the AMPA receptor.

They then determined that kibra regulated the delivery of AMPA receptors from inside the brain's nerve cells out to the synapses by first growing live brain cells from embryonic mice in a dish for two weeks and then genetically altering some of those cells to produce less kibra protein. Next, they placed the live neurons in an imaging chamber and recorded the activity of the AMPA receptors once a minute for 60 minutes. Results showed that AMPA receptors moved faster in the cells with less kibra than in control cells with normal amounts of the protein demonstrating that kibra regulates how receptors are delivered to the surface of brain cells.

The work affirms that the addition of AMPA receptors to synapses serves to strengthen connections in the brain, Huganir says, noting that most forms of learning involve the strengthening of some synapses and the weakening of others, a phenomenon known as plasticity, which is responsible for sculpting circuits in the brain that encode memory. Without kibra, this process doesn't function properly; as a result, learning and memory are compromised. Huganir hypothesizes that kibra specifically helps create a pool of receptors that is used to add receptors to synapses during learning.

Later in their study, using slices of brain from mice with or without kibra, postdoctoral fellow Lenora Volk recorded and measured electrical activity and synaptic plasticity in nerve cells, noting that mice lacking kibra showed less plasticity, a phenomenon that translates into a reduced ability to learn and recall new information, Makuch explains.

Finally, the Hopkins researchers conducted a series of behavioral studies using adult mice to compare the learning and memory of normal mice with those that made much less kibra protein. They used a well-established fear-conditioning task by placing the mice in a training chamber and exposing them to a tone and subsequent shock. After two days of training, the animals' rates of "freezing" in place -- a normal rodent response to fear -- were measured. Kibra-deficient mice took longer to learn to associate the tone with the shock than it did the others. On day three of the experiment, upon simply being placed back into the training chamber, the normal mice had a high rate of freezing, while the kibra-deficient mice had a very low rate, indicating impairments in contextual fear response and therefore, memory.

"Our work in the mammalian brain shows that kibra, required for normal brain function and associated with learning and memory, is important for regulating the trafficking of AMPA receptors," Huganir says. "In addition, as kibra has been associated with protection against early onset Alzheimer's disease, these studies may help define novel therapeutic targets for the treatment of age-related memory disorders."

This study was funded by the National Institutes of Health and the Howard Hughes Medical Institute.

Authors on the paper, in addition to Huganir, Makuch and Volk are Victor Anggono, Richard C. Johnson, and Yilin Yu, all of Johns Hopkins.

Other authors are Kerstin Duning and Joachim Kremerskothen, University Hospital Münster, Germany; Jun Xia, The Hong Kong University of Science and Technology, China; and Kogo Takamiya, University of Miyazaki, Japan.

Easily Embarrassed? Study Finds People Will Trust You More

Science Daily — Don't feel bad if tripping in public or mistaking an overweight woman for a mother-to-be leaves you red-faced. A new study from the University of California, Berkeley, suggests that easily embarrassed people are also more trustworthy and generous.

"Embarrassment is one emotional signature of a person to whom you can entrust valuable resources. It's part of the social glue that fosters trust and cooperation in everyday life," said UC Berkeley social psychologist Robb Willer, a coauthor of the study published in this month's online issue of the Journal of Personality and Social Psychology.In short, embarrassment can be a good thing.

Not only are the UC Berkeley findings useful for people seeking cooperative and reliable team members and business partners, but they also make for helpful dating advice. According to the study, subjects who were more easily embarrassed reported higher levels of monogamy.

"Moderate levels of embarrassment are signs of virtue," said Matthew Feinberg, a doctoral student in psychology at UC Berkeley and lead author of the paper. "Our data suggests embarrassment is a good thing, not something you should fight." The paper's third author is UC Berkeley psychologist Dacher Keltner, an expert on pro-social emotions.

Researchers point out that the moderate embarrassment they examined should not be confused with debilitating social anxiety or "shame," which is associated in the psychology literature with such moral transgressions as being caught cheating.

While the most typical gesture of embarrassment is a downward gaze to one side while partially covering the face and either smirking or grimacing, a person who feels shame, as distinguished from embarrassment, will typically cover the whole face, Feinberg said.

The results were gleaned from experiments that used video testimonials, economic trust games and surveys to gauge the relationship between embarrassment and pro-sociality.

In the first experiment, 60 college students were videotaped recounting embarrassing moments, such as public flatulence or making incorrect assumptions based on appearances. Typical sources of embarrassment included mistaking an overweight woman for being pregnant or a dishevelled person for being a panhandler. Research assistants coded each video testimonial based on the subjects' shame.

The college students also participated in the "Dictator Game," used in economics research to measure altruism. For example, each was given 10 raffle tickets and asked to keep a share of the tickets and give the remainder to a partner. Results showed that those who showed more significant levels of embarrassment tended to give away more of their raffle tickets, indicating greater generosity.

Researchers also surveyed 38 Americans whom they recruited through Craigslist. Survey participants were asked how often they feel embarrassed. They were also gauged for their general cooperativeness and generosity through such exercises as the dictator above the game.

In another experiment, participants watched a trained actor being told he received a perfect score on a test. The actor responded with either embarrassment or pride. They then played games with the actor that measured their trust in him based on whether he had shown pride or shame.

Time and again, the results showed that embarrassment signals people's tendency to be pro-social, Feinberg said. "You want to affiliate with them more," he said, "you feel comfortable trusting them."

So, can one infer from the results that overly confident people aren't trustworthy? While the study didn't delve into that question, researchers may look into it.

Army Developing Drones That Can Recognize Your Face From a Distance

And even recognize your intentions

By Clay Dillow

Building a 'Soft Biometric' Profile Progeny Systems Corporation via Danger Room

It’s not enough for the U.S. military to be able to monitor you from afar. The U.S. Army wants its drones to know you through and through, reports Danger Room, and it is imbuing them with the ability to recognize you in a crowd and even to know what you are thinking and feeling. Like a best friend that at any moment might vaporize you with a hellfire missile.

Of a handful of contracts just handed out by the Army, two are notable for their unique ISR capabilities. One would arm drones with facial recognition software that can remember faces so targets can’t disappear into crowds. The other sounds far more unsettling: a human behavior engine capable of stacking informant info against intelligence data against other evidence to predict a person’s intent. That’s right: the act of determining whether you are friend or foe could be turned over to the machines.

That’s a bit disquieting whether you are an insurgent warfighter or not. But back to the overarching topic at hand: The U.S. military is pulling in more ISR data than it knows what to do with these days, a lot of it useless noise that’s inconsequential to ongoing operations. And, as DR notes, the strategy in Afghanistan has changed from one of winning hearts and minds through nation building projects to targeting specific bad guys.

The hard part is keeping up with the bad guys, and that’s where Progeny Systems Corporation’s “Long Range, Non-cooperative, Biometric Tagging, Tracking and Location” system comes into play. The facial recognition layer of its technology is pretty standard: take some 2-D pictures of a target’s face, use them to build a 3-D model, and then use that 3-D model to recognize the face later.

But that’s not necessarily easy. It’s difficult enough for computers to pull off biometric facial recognition when the subject is stationary and looking straight at the camera. Toss in the many variables inherent in aerial ISR--a moving target who may be in profile or looking downward, a moving drone, low resolution cameras, etc.--and it’s a major challenge.

Progeny’s system, if it works the way the company and the Army envision it, needs just 50 pixels between the target’s eyes in a 2-D image to build the 3-D model. “Any pose, any expression, any face,” the company’s lead biometric researcher tells Danger Room. From that model stored in Progeny’s database, the system could identify the target from an even lower resolution image or video.

The closer the drone is to the subject, the better all of this works. But progeny also layers in a second kind of recognition that can work at more than 750 feet. This “soft biometric” system basically takes in a bunch of non-facial but otherwise outwardly relevant data--skin color, height and build, age, gender--to build a larger kind of model for its vision algorithms to work with. If a body is moving through the crowd, Progeny claims that a drone circling high overhead can keep track of him or her simply using this larger, whole-body identification system.

But what good is tracking if you don’t know who your enemies are? Another contract handed out to Charles River Analytics seeks to develop a human behavior engine known as Adversary Behavior Acquisition, Collection, Understanding, and Summarization (ABACUS). It mashes up all kinds of behavioral data into a system that churns out an assessment of adversarial intent, determining if a subject has enough built up resentment toward the U.S. and its aims to be a potential threat.

So pretty soon the drones may know who you are, where you’re going, and what you’re planning to do when you get there.

[Danger Room]

For the First Time, Researchers Use an Atom Interferometer to Measure Aircraft Acceleration

By Clay Dillow

Atom Interferometry Explained by Geiger et al. via arXiv

Atom interferometers are neat little devices that exploit the wave characters of atoms to make exact measurements of things like distance and or the force of gravity. But because they are fickle by nature--even the most minor vibrations distort their results--atom interferometers have been mostly limited to highly controlled experiments in underground labs or free-falling zero-g experiments. But a team of French researchers has announced today the first use of an atom interferometer to measure the acceleration of an aeroplane.

This is useful because atom interferometers are more sensitive than the inertial sensors used widely on modern aircraft. Those inertial sensors have been known to fail with potentially disastrous results, but more frequently, they cause slight errors to creep into navigation systems that must later be corrected. With no moving parts and a high degree of accuracy, atom interferometers could mitigate these problems, recording inertial effects 300 times weaker than the normal fluctuations in acceleration in a standard aircraft.

But the vibrations in an aircraft have previously made deployment of atom interferometers in planes unfeasible. That’s where Remi Geiger comes in at the Laboratoire Charles Fabry in Paris. He and his colleagues have created a system that compensates for the effects of vibrations via mechanical accelerometers that record the movements of the aircraft itself.

Using that vibration data, their system recalculates the interferometer’s data to compensate for any vibration skewing its final result. By stripping out the vibration noise, they end up with a clean, high-resolution atom interferometer result. The system could go a long way toward delivering better acceleration data to the cockpits of large jets. Geiger and company have already tested their system successfully on an Airbus A300.

But an atom interferometer that can operate free of laboratory constraints isn’t limited to jetliner applications. The researchers hope their method will lead to more precise measurements of geodesy and of gravity itself, enabling some fundamental experiments that have been previously very difficult to conduct and challenging some existing principles of physics with more and better data. More at arXiv.

[Technology]