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Signal processing: Researchers at Cogito Health are developing mathematical models to detect vocal cues that may signal depression. The last graph represents the software’s confidence level in determining depression, from the beginning to the end of a vocal recording. In this example, the data shows a very high likelihood of depression.
Credit: Cogito Health

A large-scale trial will test whether software can identify depressed patients.

MIT Technology Review, November 4, 2009, by Jennifer Chu  —  It’s a common complaint in any communication breakdown: “It’s not what you said, it’s how you said it.” For professor Sandy Pentland and his group at MIT’s Media Lab, the tone and pitch of a person’s voice, the length and frequency of pauses and speed of speech can reveal much about his or her mood.

While most speech recognition software concentrates on turning words and phrases into text, Pentland’s group is developing algorithms that analyze subtle cues in speech to determine whether someone is feeling awkward, anxious, disconnected or depressed.

Cogito Health, a company spun out of MIT based in Charlestown, MA, is building on Pentland’s research by developing voice-analysis software to screen for depression over the phone.

For years, psychiatrists have recognized a characteristic pattern in the way that many people with clinical depression speak: slowly, quietly and often in a halting monotone. Company CEO Joshua Feast and his colleagues are training computers to recognize such vocal patterns in audio samples.

Feast says the software could be a valuable tool in managing patients with chronic diseases, which often lead to depression. As part of certain disease-management programs, nurses routinely call patients between visits to ask if they are taking their medication. However, symptoms of depression are more difficult for nurses to identify. Feast says voice analysis software could provide a natural and noninvasive way for nurses to screen for depression during routine phone calls. “If you’re a nurse and you’re trying to deal with a patient with long-term diabetes, it’s very hard to tell if a person is depressed,” says Feast. “We try to help nurses detect possible mood disorders in patients that have chronic disease.”

A few years ago, the pharmaceutical giant Pfizer developed voice-analysis software to detect early signs of Parkinson’s disease. Pfizer scientists designed the software to recognize tiny tremors in speech. Such tremors offered clues to help gauge patients’ response to various medications.

In much the same way, Cogito Health’s software detects specific patterns in vocal recordings. For example, the researchers have developed mathematical models to measure a speaker’s consistency in tone, fluidity of speech, level of vocal energy, and level of engagement in the conversation (for example, whether someone responds with “uh-huh’s” or with silence). “It listens to the pattern of speech, not the words,” says Pentland, a scientific advisor to the company. “By measuring those signals in the background, you can tell what’s going on.”

The company is conducting a large-scale trial of the software by collecting hundreds of routine phone conversations between nurses and patients, with consent from both parties. After performing follow-up questionnaires to see which patients are depressed, the researchers tested the software, to see if it could accurately identify these patients. “The trials are still running, but the results are very encouraging,” says Feast, who adds that the first results will be published in 2010.

Mark Clements, a professor of electrical and computer engineering at the Georgia Institute of Technology, has analyzed vocal patterns associated with clinical depression. His lab also uses vocal cues to identify deception and anger, as well as early signs of intoxication. Clements says the benefit of Cogito Health’s approach is that it could help untrained professionals detect signs of depression. “A trained listener could detect these types of things in a person’s voice, but it’s difficult to teach a novice,” he says. “But things that are hard to hear can be detected by a computer, and have correlations with various emotional and even physical states.”

Carl Marci, director of Social Neuroscience at the Massachusetts General Hospital’s Department of Psychiatry, and another a scientific advisor to the company, says such technology could help monitor a patient’s long-term progress. “As a psychiatrist, I see patients at most once a week, sometimes once a month,” says Marci. “They’re living their lives in between, and if I had access to a data stream that captured their natural conversations, I could monitor their response to a treatment.”

Cogito Health also plans to develop software to detect other mood disorders in at-risk populations. Next year, Feast says, the company will explore vocal patterns associated with post-traumatic stress in soldiers. “We want to enable early detection of psychological distress,” says Feast, “because it has been shown that early intervention makes an enormous difference in these post-trauma situations.”

Medical Author: Benjamin C. Wedro, MD, FAAEM
Medical Editor: Melissa Conrad Stöppler, MD
MedicineNet.com

FAQs – About Your Kidneys

What are the kidneys?

The kidneys play key roles in body function, not only by filtering the blood and getting rid of waste products, but also by balancing levels of electrolytes in the body, controlling blood pressure, and stimulating the production of red blood cells.

The kidneys are located in the abdomen toward the back, normally one of each side of the spine. They get their blood supply through the renal arteries directly from the aorta and send blood back to the heart via the renal veins to the vena cava. (The term “renal” is derived from the Latin name for kidney.)

The kidneys have the ability to monitor the amount of body fluid, the concentrations of electrolytes like sodium and potassium, and the acid-base balance of the body. They filter waste products of body metabolism, like urea from protein metabolism and uric acid from DNA breakdown. Two waste products in the blood can be measured: blood urea nitrogen (BUN) and creatinine (Cr).

When blood flows to the kidney, sensors within the kidney decide how much water to excrete as urine, along with what concentration of electrolytes. For example, if a person is dehydrated from exercise or from an illness, the kidneys will hold onto as much water as possible and the urine becomes very concentrated. When adequate water is present in the body, the urine is much more dilute, and the urine becomes clear. This system is controlled by renin, a hormone produced in the kidney that is part of the fluid and blood pressure regulation systems of the body.

Kidneys are also the source of erythropoietin in the body, a hormone that stimulates the bone marrow to make red blood cells. Special cells in the kidney monitor the oxygen concentration in blood. If oxygen levels fall, erythropoietin levels rise and the body starts to manufacture more red blood cells.

After the kidneys filter blood, the urine is excreted through the ureter, a thin tube that connects it to the bladder. It is then stored in the bladder awaiting urination, when the bladder sends the urine out of the body through the urethra.

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What causes kidney failure?

Kidney failure can occur from an acute situation or from chronic problems.

In acute renal failure, kidney function is lost rapidly and can occur from a variety of insults to the body. The list of causes is often categorized based on where the injury has occurred.

Prerenal causes (pre=before + renal=kidney) causes are due to decreased blood supply to the kidney. Examples of prerenal causes are:

  • Hypovolemia (low blood volume) due to blood loss
  • Dehydration from loss of body fluid (vomiting, diarrhea, sweating, fever )
  • Poor intake of fluids
  • Medication, for example, diuretics (“water pills”) may cause excessive water loss.
  • Loss of blood supply to the kidney due to obstruction of the renal artery or vein.

Renal causes (damage directly to the kidney itself) include:

Post renal causes (post=after + renal= kidney) are due to factors that affect outflow of the urine:

  • Obstruction of the bladder or the ureters can cause back pressure when there is no place for the urine to go as the kidneys continue to work. When the pressure increases enough, the kidneys shut down.
  • Prostatic hypertrophy or prostate cancer may block the urethra and prevents the bladder from emptying.
  • Tumors in the abdomen that surround and obstruct the ureters.
  • Kidney stones

Chronic renal failure develops over months and years. The most common causes of chronic renal failure are related to:

Less common causes:

What are the symptoms of kidney failure?

  • In the beginning, kidney failure may be asymptomatic (not producing any symptoms). As kidney function decreases, the symptoms are related to the inability to regulate water and electrolyte balances, to clear waste products from the body, and to promote red blood cell production. Lethargy, weakness, shortness of breath, and generalized swelling may occur. Unrecognized or untreated, life-threatening circumstances can develop.
  • Metabolic acidosis, or increased acidity of the body due to the inability to manufacture bicarbonate, will alter enzyme and oxygen metabolism, causing organ failure.
  • Inability to excrete potassium and rising potassium levels in the serum (hyperkalemia) is associated with fatal heart rhythm disturbances (arrhythmias).
  • Rising urea levels in the blood (uremia) can affect the function of a variety of organs ranging from the brain (encephalopathy) with alteration of thinking, to inflammation of the heart lining (pericarditis), to decreased muscle function because of low calcium levels (hypocalcemia).
  • Generalized weakness can be due to anemia, a decreased red blood cell count, because lower levels of erythropoietin do not adequately stimulate the bone marrow. A decrease in red cells equals a decrease in oxygen-carrying capacity of the blood, resulting in decreased oxygen delivery to cells for them to do work; therefore, the body tires quickly. As well, with less oxygen, cells more readily use anaerobic metabolism (an=without + aerobic=oxygen) leading to increased amounts of acid production that cannot be addressed by the already failing kidneys.
  • As waste products build in the blood, loss of appetite, lethargy, and fatigue become apparent. This will progress to the point where mental function will decrease and coma may occur.
  • Because the kidneys cannot address the rising acid load in the body, breathing becomes more rapid as the lungs try to buffer the acidity by blowing off carbon dioxide. Blood pressure may rise because of the excess fluid, and this fluid can be deposited in the lungs, causing congestive heart failure.

How is kidney failure diagnosed?
Diagnosis of kidney failure is confirmed by blood tests measuring the buildup of waste products in the blood. BUN and creatinine become elevated, and the glomerular filtration rate decreases. This is the rate with which blood is filtered through the kidneys and can be calculated based upon the creatinine level, age, race, and gender.

Urine tests may be done to measure the amount of protein, detect the presence of abnormal cells, or measure the concentration of electrolytes. Protein in the urine is not normal and can be a clue that damage to the kidneys has occurred. Abnormal aggregations of red and white blood cells called casts can be seen in the urine with kidney disease. Comparing the concentrations of electrolytes in the blood and urine can help decide whether the kidneys are able to appropriately monitor and filter blood.

Other tests are used to diagnose the type of kidney failure. Abdominal ultrasound can assess the size of the kidneys and may identify whether any obstruction exists. Biopsy of the kidney uses a thin needle that is placed through the skin into the kidney itself to get bits of tissue to examine under the microscope.
What is the treatment for kidney failure?
Prevention is always the goal with kidney failure. Chronic disease such as hypertension and diabetes are devastating because of the damage that they can do to kidneys and other organs. Lifelong diligence is important in keeping blood sugar and blood pressure within normal limits. Specific treatments are dependent upon the underlying diseases.

Once kidney failure is present, the goal is to prevent further deterioration of renal function. If ignored, the kidneys will progress to complete failure, but if underlying illnesses are addressed and treated aggressively, kidney function can be preserved, though not always improved.

Diet

Diet is an important consideration for those with impaired kidney function. Consultation with a dietician may be helpful to understand what foods may or may not be appropriate.

Since the kidneys cannot easily remove excess water, salt, or potassium, they may need to be consumed in limited quantities. Foods high in potassium include bananas, apricots, and salt substitutes.

Phosphorus is a forgotten chemical that is associated with calcium metabolism and may be elevated in kidney failure. Too much phosphorus can leech calcium from the bones and cause osteoporosis and fractures. Foods with high phosphorus content include milk, cheese, nuts, and cola drinks.

Medications

Medications may be used to help control some of the issues associated with kidney failure.

Once the kidneys fail completely, the treatment options are limited to dialysis or kidney replacement by transplantation.

Medscape.com, November 3, 2009, by  Yael Waknine  –  The US Food and Drug Administration (FDA) has issued a warning about the incretin-mimetic exenatide (Byetta, Amylin Pharmaceuticals, Inc) the same day the agency approved an expanded indication for the drug, allowing its first-line use along with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus.

The warning includes 78 postmarketing reports of kidney dysfunction (including acute renal failure and insufficiency), received between April 2005 and October 2008, in 6.6 million users. “Some cases occurred in patients with pre-existing kidney disease or in patients with one or more risk factors for developing kidney problems,” according to an alert sent yesterday from MedWatch, the FDA’s safety information and adverse event reporting program.

The FDA emphasizes that exenatide should not be used in patients with severe renal impairment (creatinine clearance < 30 mL/minute) or end-stage renal disease, and it advises caution during initiation of therapy and dose increases in patients with moderate renal dysfunction (creatinine clearance, 30 – 50 mL/minute).

Patients receiving exenatide should be carefully monitored for signs and symptoms of altered renal function, including increased serum creatinine, changes in urination, unexplained swelling in the extremities, blood pressure increases, lethargy, changes in appetite or digestion, or the emergence of a dull ache in the mid- to lower back.

The agency notes that alterations in kidney function may also occur as a consequence of diabetes itself, other chronic conditions (eg, pancreatitis and hypertension), or concomitant use of certain medications (nonsteroidal anti-inflammatory drugs, diuretics, and antihypertensives). Discontinuation of exenatide should be considered if kidney dysfunction cannot be explained by these or other causes such as nausea, vomiting, and dehydration.

The approval of exenatide monotherapy was based on clinical data showing that 3 months of treatment at doses of 5 or 10 μg significantly reduced mean hemoglobin A1C levels by 0.7% and 0.9%, respectively, and yielded mean weight losses of 6.0 and 6.4 pounds, respectively.

The most commonly reported adverse event was nausea, which occurred in 3% of patients receiving the 5-μg dose and 13% of those taking 10 μg of exenatide daily. Hypoglycemia was reported at rates of 5% and 4%, respectively; no severe hypoglycemic events were noted.

Exenatide was previously approved as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who have not achieved adequate glycemic control on metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione.

More information is available on the FDA’s MedWatch Web site.

Adverse events related to the use of exenatide should be communicated to the FDA’s MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

Harvard Medical School, November 3, 2009  —  As with so many things, when it comes to neck pain, an ounce of prevention may be worth a pound of cure. It’s true that some causes of neck pain such as age-related wear and tear are not under your control. On the other hand, there are many things you can do to minimize your risk. One place to start is to look at how you sleep and what effect this may have on neck pain. 

Getting in the best position 

Two sleeping positions are easiest on the neck: on your side or on your back. If you sleep on your back, choose a rounded pillow to support the natural curve of your neck, with a flatter pillow cushioning your head. This can be achieved by tucking a small neck roll into the pillowcase of a flatter, softer pillow, or by using a special pillow that has a built-in neck support with an indentation for the head to rest in. Here are some additional tips for side- and back-sleepers: 

Try using a feather pillow, which easily conforms to the shape of the neck. Feather pillows will collapse over time, however, and should be replaced every year or so. 

Another option is a traditionally shaped pillow with “memory foam” that conforms to the contour of your head and neck. Some cervical pillows are also made with memory foam. Manufacturers of memory-foam pillows claim they help foster proper spinal alignment. 

Avoid using too high or stiff a pillow, which keeps the neck flexed overnight and can result in morning pain and stiffness. 

If you sleep on your side, keep your spine straight by using a pillow that is higher under your neck than your head. 

When you are riding in a plane, train, or car, or even just reclining to watch TV, a horseshoe-shaped pillow can support your neck and prevent your head from dropping to one side if you doze. If the pillow is too large behind the neck, however, it will force your head forward. 

Sleeping on your stomach is tough on your spine, because the back is arched and your neck turned to the side. Preferred sleeping positions are often set early in life and can be tough to change, not to mention that we don’t often wake up in the same position in which we fell asleep. Still, it’s worth trying to start the night sleeping on your back or side in a well-supported, healthy position.

Beyond sleep position

Emerging research suggests that not just sleep position, but sleep itself, can play a role in musculoskeletal pain, including neck and shoulder pain. In one 2008 study, researchers compared musculoskeletal pain in 4,140 healthy men and women with and without sleeping problems. Sleeping problems included difficulty falling asleep, trouble staying asleep, waking early in the mornings, and non-restorative sleep. They found that people who reported moderate to severe problems in at least three of these four categories were significantly more likely to develop chronic musculoskeletal pain after one year than those who reported little or no problem with sleep. One possible explanation is that sleep disturbances disrupt the muscle relaxation and healing that normally occur during sleep. Additionally, it is well established that pain can disrupt sleep, contributing to a vicious cycle of pain disrupting sleep, and sleep problems contributing to pain.

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Genomic and proteomic analysis has found a new evolutionary mechanism that accounts for some of the biological complexity of human beings. (Credit: iStockphoto/Liang Zhang)

ScienceDaily (Nov. 4, 2009) – A painstaking analysis of thousands of genes and the proteins they encode shows that human beings are biologically complex, at least in part, because of the way humans evolved to cope with redundancies arising from duplicate genes.

“We have found a specific evolutionary mechanism to account for a portion of the intricate biological complexity of our species,” said Ariel Fernandez, professor of bioengineering at Rice University. “It is a coping mechanism, a process that enables us to deal with the fitness consequences of inefficient selection. It enables some of our proteins to become more specialized over time, and in turn makes us more complex.”

Fernandez is the lead author of a paper slated to appear in the December issue of the journal Genome Research. The research is available online now.

Fernandez said the study drew from previous findings by his own research group and from seminal work of Michael Lynch, Distinguished Professor of Biology at Indiana University and a recently elected a fellow of the National Academy of Science. Lynch’s work has shown that natural selection is less efficient in humans as compared with simpler creatures like bacteria. This “selection inefficiency” arises from the smaller population size of humans as compared with unicellular organisms.

“In all organisms, genes get duplicated every so often, for reasons we don’t fully understand,” Fernandez said. “When working efficiently, natural selection eliminates many of these duplicates, which are called ‘paralogs.’ In our earlier work, we saw that an unusual number of gene duplicates had survived in the human genome, which makes sense given selection inefficiency in humans.”

In prior research on protein structure, Fernandez’s team found that some proteins are packaged more poorly than others. Moreover, they found that the least-efficiently packed proteins are structurally stable only when they bind with partner proteins to form complexes.

“These poorly packed proteins are potential troublemakers when gene duplication occurs,” Fernandez said. “The paralog encodes more copies of the protein than the body needs. This is called a ‘dosage imbalance,’ and it can make us sick. For instance, dosage imbalance has been implicated in Alzheimer’s and other diseases.”

Given selection inefficiency, Fernandez knew that paralogs encoding poorly packed proteins could remain in the human genome for quite a while. So he and graduate student Jianpeng Chen decided to examine whether gene duplicates had remained in the genome long enough for random genetic mutations to affect the paralogs dissimilarly. Fernandez and Chen, now a senior researcher in Beijing, China, cross-analyzed databases on genomics, protein structure, microRNA regulation and protein expression in such troublesome paralogs.

“The longer these duplicate genes stick around due to inefficient selection, the more likely they are to suffer a random mutation,” Fernandez said. “Portions of every gene act to regulate protein expression — by binding with microRNA, for example. We found numerous instances where random mutations had caused paralogs to be expressed dissimilarly, in ways that removed detrimental dosage imbalances.”

Lynch said one aspect of Fernandez’s research that is potentially groundbreaking is the observed tendency of proteins to evolve a more open structure in complex organisms.

“This observation fits with the general theory that large organisms with relatively small population sizes — compared to microbes — are subject to the vagaries of random genetic drift and hence the accumulation of very mildly deleterious mutations,” Lynch said.

In principle, he said, the accumulation of such mutations may encourage a slight breakdown in protein stability. This, in turn, opens the door to interactions with other proteins that can return a measure of that lost stability.

“These are the potential roots for the emergence of novel protein-protein interactions, which are the hallmark of evolution in complex, multicellular species,” Lynch said. “In other words, the origins of some key aspects of the evolution of complexity may have their origins in completely nonadaptive processes.”

Fernandez said the research reveals how increasingly specialized proteins can evolve. He drew an analogy to a business that hires two delivery drivers that initially cover the same parts of town but eventually specialize to deliver only to specific neighborhoods.

“Eventually, even if times become tough, you cannot lay off either of them because they each became so specialized that your company needs them both,” he said.

The more simple a creature is, the fewer specialized proteins it possesses. Humans and other higher-order mammals need many specialized proteins to build the specialized tissues in their skin, skeleton and organs. Even more specialized proteins are needed to maintain and regulate them. This complexity requires that the duplicates of the original jack-of-all-trades gene be retained, but this does not happen unless selection is inefficient. This is frequently a point of contention between proponents of evolution and intelligent design.

Fernandez and Chen looked at duplicate genes across the human genome and found that the more poorly packed a protein was, the more likely it was to be distinguished through paralog specialization.

“This supports the case for evolution because it shows that you can drive complexity with random mutations in duplicate genes,” Fernandez said. “But this also implies that random drift must prevail over Darwinian selection. In other words, if Darwinian selection were ruthlessly efficient in humans — as it is in bacteria and unicellular eukaryotes — then our level of complexity would not be possible.”

The research is supported by the National Institutes of Health.