At the same time, our culture is obsessed with youth - Americans drop huge amounts of money on products that are designed to make us seem younger than we are, and on top of that, behavior resembling that of a normal 3-6 year-old seems to be more and more common in adults. And unlike in some of the few remaining cultures in which older people are respected and revered for their life experience and wisdom, we quickly cast our older family members aside and often ignore them; instead of valuing time spent with them because of what we might learn from them, we avoid spending that time because we see them mostly as a reminder of our own mortality.

The second problem may be hard to change, because it involves changing cultural norms, but the first problem is societal and absolutely must be addressed, because of the financial burden on society that will eventually result from not fixing it. We are already inching up retirement age for social security benefits, so it would be good if we could keep people healthy enough to work longer. Certainly, quality-of-life issues have become more and more important in medical research in recent years. But although we say that quality of life is now an important consideration in health care, our development of more and more treatments of disease designed to stave off death, is simultaneously and ironically reducing quality of life for many people through over treatment.

What receives the news and attention is not public health measures we already know we could do (with some money) to raise the quality of life for older people, but rather any research result that suggests that an anti-aging pill is right around the corner - our continuing obsession with a Fountain of Youth. Great for you (perhaps), bad for society. This New Yorker article from two years ago spells out just how important - and underserved - geriatrics care is becoming.

While there is money for aging research, which even has its own institute within the National Institutes of Health (funding groups such as this), there is a huge shortage of primary care physicians interested in specializing in geriatrics, which focuses on improving quality of life for people right now, and is of course is one of the fastest-growing needs in health care. One obvious way to address shortages in primary and geriatric care would be to provide incentives for doctors to go into these areas through loan forgiveness and/or subsidizing medical school. So far, though, this has yet to happen.

What funding there is for quality-of-life versus quantity-of-life research is not at the same scale; for example, an advertised grant for “Improving the Quality of Life for Persons Living in Nursing Homes” was for a paltry $10,000. (The situation may be improving in the changing political climate, though - NIH currently has a grant program for $500,000 for up to five years to address the issue of reducing healthcare costs while increasing quality of life.)

Technically, the imbalance in funding priorities shouldn’t be surprising. After all, who provides the funding for most research? Typically, of course, it is powerful older men who think they should be able to live forever. This attitude plays a big part in our current unsustainable trajectory in health care.

Ironically, if all the research into new drugs to extend lifespan comes to fruition, it will just create more top-heavy demographics and strain our resources further, contributing to the system’s unsustainability. For though the stated goal of the research is generally “to extend healthy and productive human lifespan,” in the end, what have previous extensions of lifespan really given us? On a large scale, just more new diseases to spend billions combating, and thus more healthcare costs to add to the pile. That’s why aging research and funding should mainly focus on better comfort for those of us lucky enough to reach an age at which we will suffer the typical ills naturally associated with aging, not simply on extending our lifespan.

The question remains, which to my knowledge no one has bothered to attempt to answer: How many medical bankruptcies are caused by insurance companies refusing to pay what they actually owe, who instead are sticking it to patients who are too worried with their medical problems to focus on the ridiculous amount of paperwork that they generate to obfuscate the fact that they are screwing us?

What’s amazing is that the Senate report apparently only touches on the manipulation of out-of-network reimbursements to charge patients more. How about the slew of bills my company sent along to me last year for “out-of-network” charges, that were actually, every one, in-network? When will these “reports” start calling out the companies for consistently denying coverage to all their paying customers except for those persistent enough to demand over and over again what the company already covers?

At a hearing this afternoon, Rockefeller’s panel is slated to air allegations by a former industry insider that insurers have put profits before people’s health.

The fact that this is treated as news just proves how incredibly clueless our national leaders, the ones supposedly reforming the system, are about what it’s like in the trenches for those of us without primo government insurance and large personal staffs. This, my friends, is the big reason why our congress is making such a botch out of fixing the system, when the solutions are so obvious to those of us living our lives outside the beltway. Hopefully another reason isn’t simply that they want their insurance-business buddies to continue getting rich off other peoples’ hardship and misery. But given how the “reform” movement is going right now, it would be foolish to rule that out.

Of course the enthusiastic boosters of perfect lawns don’t want you to think about the downside of all those billions of acres of grass, most of which is apparently there simply to be looked at adoringly. Here is a laughable quote from the Lawn Care Association of Pennsylvania web site:

The U.S. Congress noted the benefits of grass and other vegetation in a 1990 Farm Bill: “…low growing dense perennial turfgrass sod in urban areas and communities can aid in reducing carbon dioxide missions, mitigating the heat island effect, and reducing energy consumption, thus contributing to efforts to reduce global warming trends.”

They then go on a couple paragraphs later to recommend: “Mow at the highest recommended height and mow often, never removing more than one-third of the left surface.”

Of course it is convenient for them to ignore the fact that frequent mowing of these “environmentally friendly” lawns will lead to a lot more carbon dioxide emissions than they are absorbing. The as-of-yet unregulated two-stroke engines that predominate the lawn care industry produce a huge amount of pollutants such as carbon monoxide, hydrocarbons and nitrogen oxides, in addition to the CO2. Small engines are now the worst polluters, contributing around 25% of the nation’s pollution from moving sources (including cars and trucks), according to the EPA.

This perversely has spawned “green lawn care” businesses that promise to give you your perfect lawn with environmentally friendly electric and biodiesel-fueled machines. Although these methods chip away at both the emissions and irritating ambient noise produced by lawn care, they don’t address the root idiocy: apparently, as much as we want to go “green,” you can’t ask us to give up our lawns (which only wear that color as a disguise).

The EPA tells us (as of 1996, apparently the last time this document was updated) that cleaner, greener lawn machines are on the way - although new emission standards will not actually be imposed for lawn equipment until 2011. Until then, we all should make lawn care more ecologically friendly by taking such important steps as avoiding gasoline spills when filling our massive mowers. That was originally meant as a sarcastic statement, but unbelievably, the EPA estimates 17 million gallons of gasoline per year (more than was spilled by the Valdez) are spilled just in the refueling of power lawn equipment. Wow.

Okay, farther down the document they finally mention the possibility of using a push mower and even eliminating part of the lawn by replacing it with trees, native plants, etc. That, frankly, would create a true CO2 sink - a garden of plants that don’t require petroleum in the form of carbon-emitting gasoline motors and fertilizers for maintenance.

And even the “green lawn” types promote electric equipment as opposed to strictly mechanical, even though people are routinely seen cutting a postage-stamp lawn with a power - even riding - mower. Undoubtedly some of the people doing this are then hopping in their SUV’s and driving to the gym so they can get in a real workout.

The cycle starts in the spring and continues all summer for lawnophiles: you call “TruGreen” Chemlawn to come on over and drench your kids’ play area thoroughly with pesticides that will end up as runoff into our lakes and rivers, fertilize (ditto), and then you water every 2-3 days, alternating with mowing every 2-3 days. Then you dump the grass clippings into garbage bags and have them taken far, far from your lawn.

Here’s a law we should have that all “personal freedom” (except of course when it comes to abortion and who you have sex with) conservatives would love to hate: if your lawn is less than 2000 square feet, no power mowers allowed. Not only would we dramatically reduce noise and air pollution, the latter far more dramatically than we will with the incremental raising of emission standards, but instead of being sent to permanent anoxic stasis in the landfill, a lot of grass clippings would stay right where they are needed to fertilize the living grass, reducing chemical pollution from all the gratuitous fertilizer.

And as a bonus, you could then skip your summer gym membership and supplement your mechanical mowing with more walking, which will further reduce pollution, save oil, and make you a little less fat at the end of the summer, all for free. And your neighbors will love you (even if you don’t know them).

However, as in most pharmaceutical situations, the conservative action is not to take the extra drug (whether it be novel chemical or “essential” vitamin), because although we think we know that anything marketed as a supplement must be good for us, this is by no means the case. We still know next to nothing about how the human body works even when we’re not messing with it by adding supplements to the mix.

The idea behind the latest caution is that chemotherapy works to destroy cancer cells through the creation of reactive oxygen species (ROS - of which the infamous “free radicals” are a major type). So, if the body is flooded with extreme amounts of antioxidants such as vitamins C and E, it is possible the chemo will not be as effective.

Of course, the flip side of this is that perhaps the antioxidants protect non-cancer cells, which could reduce side-effects associated with chemotherapy. But any positive effect has yet to be studied, and if you are protecting cancer cells along with the cells you like, really what is the point of chemotherapy in the first place? (A cynical answer to this question can actually be found on this site, but it is not really relevant to the question at hand.)

What data we do have continue to challenge the popular notion that massive supplement use is beneficial. When we introduce large amounts of a chemical into our bodies, even chemicals we know can have a useful function at much lower levels (”too much of a good thing” applies pretty much to anything we ingest, even water), we are creating a novel environment to which humans have not had a chance to respond evolutionarily. Logically, the chances that interfering with more natural bodily functions in this way will create problems are much, much higher than the chances that we are smugly improving on nature.

Although cancer treatment is a special case that has yet to be definitively tested, the logic of the doctors concerned about the practice of massive antioxidant use during treatment cannot be denied. And the negative effects of antioxidants on exercise physiology are not a special case.

So do yourself a favor, even if you are lucky enough not to be someone undergoing chemotherapy at this moment: lay off the supplements, and eat your vegetables.

But the fact is that the more we study cancer, the more complicated it gets. It’s been decades since we were promised an imminent cure by well meaning researchers, but although treatments have advanced, it is becoming clearer that a wide-encompassing cure is about as likely as a cure for the common cold, for much the same reasons: cancer is not one disease, but a catch-all term that we use to describe hundreds or thousands of variant conditions (not all of which are actually fatal). Even two cancer patients with similar pathologies (based on what we currently know) can have hugely different outcomes, for which we have no adequate explanation. The fact is, cancer treatment, though becoming somewhat more sophistocated, is still largely a guessing game.

One way to understand this is to realize that cancer is caused by a large variety of genetic issues interacting with a large (and unreplicable) suite of environmental conditions. The BRCA genes alone, which have been implicated in hormone-mediated cancers such as breast and prostate cancer, have over a thousand known mutations, most of which we do not understand. (Of course it doesn’t help that a single company, Myriad Genetics, has received a patent on these genes, which means no one is allowed to study them without their permission.) That is, it is possible for someone with a BRCA mutation never to get cancer, or to get it very young. What happens depends on the particular mutation and its complicated interactions with any potential carcinogen the person has ever been exposed to.

Researchers are getting better slowly at tailoring treatment to specific pathologies, but make no mistake, there is a long way to go. One problem that delays progress is inertia in the medical establishment to change treatment regimens that have become established dogma. Although doctors are quick to pick up on a new drug that seems to be effective in medical trials - the pharmaceutical companies make sure they are informed of every one - they are much slower to stop using a drug that has been shown to be ineffective for patients with a particular pathological profile, because there is not an equal profit-driven push in the other direction. Quite the opposite, in fact.

Two examples: It is now fairly definitive that anthracyclines (such as Adriamycin) are only effective in breast cancer patients that are positive for the HER2 receptor (Slamon & Press, 2009):

Over the past 15 years, a substantial amount of clinical data from multiple individual studies has indicated that the incremental benefit from adjuvant anthracycline-based therapies is largely restricted to the HER2-positive subgroup of human breast cancers.

But you can be sure that many oncologists will continue to encourage HER2 negative women to take these potentially dangerous drugs.

By the same token, it was also established years ago that CMF chemotherapy adds no treatment value on top of hormone therapy for hormone-positive breast cancers (Ejlertsen et al., 2006). Yet, one oncologist at a top cancer center was offering it a year ago (and perhaps still is) as a reasonable option to women with this pathology.

This is no help to progress in cancer treatment. But continued talk of a “cure” is no help to patients, who ironically can have both overly pessimistic and overly optimistic views of their prognoses. They can be overly pessimistic because when many people hear the word “cancer,” they imagine an automatic death sentence. They can be overly optimistic because after they have endured an often-hellish treatment, they may be under the impression that the cancer has been eradicated, when in fact it is impossible ever to know if this is the case.

Instead of swinging between these mythic extremes, we need to change the culture of how we think about cancer, in the same way that we need to change the culture of health care in general in order to end up with an American system of sustainable, universal health care. Overscreening and overtreatment have become the norm as we have headed farther and farther along the path of for-profit medicine. Fear of the word “cancer” and use of the word “cure” dovetail nicely with the medical profit motive as we continue on our unsustainable course toward a healthcare train wreck. Nearly 50 individual treatments of prostate cancer to save one life is great for charity fundraising and pharmaceutical business but lousy for our health.

The fact is, we all have cancer. Our tumor-supressing proteins are constantly working to keep it from reaching a pathological level, but for many, many reasons, most unknown, the system often fails and cancer then spreads to an alarming degree. But most of us should be thinking in terms of management of a condition with the potential to cause us problems in the future, similar to the way we manage diabetes, rather than hysterically reaching for the knife every time a few cancer cells are discovered by our increasingly sensitive scanning technology. Some recommend not being screened at all in order to avoid unnecessary worry, but wouldn’t it make the most sense for many of us to go ahead and screen, but then think in terms of monitoring instead of treatment as a first step when pre-tumorous cancer is detected?

It will take a lot of effort to change the healthcare-for-profit, magic-pill-for-everything-as-long-as-you-can-pay culture we have dug ourselves deeply into. But if we don’t, Americans will go back to dying from what are currently considered easily preventable and treatable Third-World diseases, in addition to the confounding diseases of wealth that we pour so many billions into now.

References

Ejlertsen, B, Mouridsen, H.T., Jensen, M., Bengtsson, N., Bergh, J., Cold, S., Edlund, P., Ewertz, M., de Graaf, P.W., Kamby, C., Nielsen, D.L. 2006. Ovarian ablation compared with cyclophosphamide, methotrexate, and fluorouracil: Similar efficacy from a randomized comparison in premenopausal patients with node-positive, hormone receptor-positive breast cancer. J Clin Oncol. 24:4956-4962.

Slamon, D.J., and Press, M.F., 2009. Alterations in the TOP2A and HER2 genes: association with adjuvant anthracycline sensitivity in human breast cancers. Journal of the National Cancer Institute 101(9):615-618

If an artist is focused on making an artistic connection, does it prevent him from making connections on a personal level? Sondheim seems to be saying that is often the case, as both his main characters have been unsuccessful romantically, while making artistic breakthroughs.

Sondheim’s fictional version of Georges Seurat, the impressionist painter of the late 19th century, strives for order, design, tension, balance, and harmony in his work. The real Seurat developed a new technique that became known as “pointillism,” based on the scientific notion that the human eye blends separate pixels of different color into one overall color. For example, many pixels of red and blue next to each other look purple to the eye, as if the colors were directly mixed themselves. (This principle is what allows us to perceive so many different shades of color on televisions and computer monitors, which display all their information in pixels.) The fictional Seurat has broken through to something new in art, but generally his art is not successful; it is perceived as bizarre. Without support from other people, Seurat is left with only his own belief that he is doing something significant. But his obsession with his work sucks him into it, making him oblivious to the few people who care about him.

The artist of the second act is Seurat’s fictional great-grandson, George, who is struggling to do something new with his art. While the Seurat of the first act abandoned human relationships for the sake of his innovative art, George’s world a hundred years later is one in which he must develop those relationships to allow him to produce his own visions, which require substantial funding. More fundamentally though, he is suffering from artists’ block, unable to see his way to produce something new. To simply a rehash previous ideas would not be a way to make true art.

The themes in the show do not apply only to artists. Any of us might understand the importance of order, design, tension, balance, and harmony in our lives:

• Order: We all arrange the pieces of our lives into a narrative, “putting it together.”
• Design: Without design, what coherent accomplishments are possible? An aimless life could be considered a wasted life.
• Tension: We all have tasks we need to accomplish, improvements to make, ways in which we want to improve ourselves and our lives. This is was drives us to accomplish more.
• Balance: How do we reconcile our internal, personal needs and those of others with whom we have relationships? Our internal world, which can never be completely known by another, must balance in someway with our life in the external world in which we interact with others.
• Harmony: It is possible for all of us to be at peace with how these elements function in our lives. This is the willingness to be happy with how it has all meshed.

In his brilliant music for “Sunday in the Park with George,” Sondheim illustrates these concepts. In one example, there is a recurring musical theme that is a succinct representation of both pointillism and the artist’s struggle with the components of his art, particularly expressing tension that needs to be resolved into harmony. Listen to this short theme below:

The last note of the theme is the leading tone (major seventh note of the scale), which uniquely holds tension. This note, more than any other in the scale, aches to resolve to the tonic (first note of the scale). But it does not do so, leaving the tension hanging, the sequence unfinished. This represents the tension for Seurat in always working intently on something that has yet to be finished, that cuts him off from engaging successfully with people apart from through his art. The idea is eloquently expressed in his song “Finishing the Hat.”

There were shades of Sondheim’s Seurat character reflected in Calvin Tomkins’ profile of the artist Bruce Nauman in a recent New Yorker. Like the fictional modern artist George, Nauman says:

…he hoped he’d figure out how to make art without such a struggle, but it never happened. “My dad once said, ‘You don’t have to reinvent the wheel every day,’ but I think you do…Maybe not every day, but pretty often.”

And, like Sondheim’s Seurat, Nauman’s relationships suffered because of his art. His first wife could not “…accept the emotional distance that her husband seemed to require. ‘My feelings are in my work,’ he told her…Bruce was a supportive husband and attentive father, she said, but ‘he was an artist first.’”

Sondheim’s Seurat died a lonely man. Nauman, by contrast, seems to have found someone who can balance with the demands of his art: another artist, Susan Rothenberg. Perhaps because she has similar passions she has empathy for his artistic needs, and so they have found harmony:

I’ve finally realized I don’t need to know the stuff Bruce is unable to tell me. I think we love each other very much…I’m very satisfied with hm, and very happy living about ninety-two percent of my life by myself. I don’t think I’ll ever know Bruce, but he is mine…

The CRP is more complicated in its combination of benefits to taxpayers vs. just farmers. Although it is sometimes lumped in with the above programs, it has stricter requirements about what happens to the land than say, the rice-growers subsidies, and it does have some documented conservation benefits.

Part of the CRP’s problem is that it is not clear what its purpose really is. Is the point to subsidize farmers, or to conserve habitat? The USDA seems to like to emphasize the latter on their web site, and it is true that cropland, typically monoculture, has lower species diversity than the CRP lands which has much more diverse vegetation (King & Savidge, 1995). But based on the subsidy levels, which have been higher than they need to be for the value of the land (Smith, 1995), the former seems to be the true function.

Of course the other aspect of the program that undermines its conservation value is that contracts are typically 10-15 years, after which the farmer can choose to put the conserved land back into agricultural production, thus obliterating all the conservation gains that have been made in the decades since the program began.

About a year ago, in fact, big agriculture and farm state senators were putting pressure on Secretary of Agriculture Ed Schafer to allow early release (without penalty) from lands contracted under the program, in order for farmers to cash in on the ethanol boom, which was famously driving up grain prices until our recent recession kicked in. Fortunately, Schafer made his decision when prices were already beginning to fall back, and he refused to alter the agreements.

Another unintended effect of the program, though, has been that as lands in the CRP increased, farmers have developed new farmlands (Wu, 2000), presumably from land that had been more ecologically diverse. This loss of acres contributing to biodiversity is not of course mentioned by proponents of the program that promote its conservation value.

The recession will not last forever, and when agricultural subsidies and crop prices get back to their destructive combination, it seems certain that millions of acres will be brought out of the CRP and converted back to cropland. Although biodiversity on these lands will be an obvious casualty, at least perhaps soil degredation can be slowed down a bit. Follett et al. (2009) have determined that no-till corn production could help maintain soil organic carbon levels. Then perhaps when the government finally wakes up and gets rid of the disastrous ethanol subsidies, the lands returned to the program would not take so long to become real habitat again.

But don’t expect the USDA to think ahead and take steps to require the beneficial practice. That (but apparently not generous subsidies) would certainly interfere with the “freedom to farm.”

References

Follett, R.F., Varvel, G.E., Kimble, J.M., and Vogel K.P., 2009. No-till corn after bromegrass: effect on soil carbon and soil aggregates. Agronomy Journal 101(2)261-268.

Johnson, D.H. and Schwartz, M.D., 1993. The Conservation Reserve Program and grassland birds. Conservation Biology 7(4):934-937.

King, J.W. and Savidge, J.A., 1995. Effects of the Conservation Reserve Program on wildlife in southeast Nebraska. Wildlife Society Bulletin 23(3):377-385.

Smith, R.B.W., 1995. The Conservation Reserve Program as a least-cost land retirement mechanism. American Journal of Agricultural Economics 77(1):93-105.

Wu, J., 2000. Slippage effects of the Conservation Reserve Program. American Journal of Agricultural Economics 82(4):979-992.

People from both extreme ends of the political spectrum claim to have logically thought through their positions, but that process always carries bias along with it. The root of our social biases is in-group vs. out-group mentality - how we distinguish those ‘with’ us from those ‘against.’

The power of this effect is striking. Asburn-Nardo and colleagues (2001) showed that anti-out-group biases emerge quickly even in the absence of any negative information about the out-group; it is strong even when groups are randomly assigned. This unconscious response is rooted in the limbic system of the brain, which also is associated with emotions such as fear. We cannot truly control our emotions, and likewise it is not a conscious process when we notoriously assimilate weak evidence to support our views, and ignore strong evidence that would refute them.

This response is likely rooted in humans’ evolutionary history as a social species (Tobena et al., 1999). When so much depends upon interactions with other individuals, shorthand for ‘us’ versus ‘them’ is important. Humans love to make rules, probably because rules help us to navigate society.

The less we interact face-to-face, the more of a problem bias becomes, though, so conflict due to ‘us’ vs. ‘them’ mentality is not going to go away any time soon. At the same time, a lot of people are successful much of the time at suppressing unconscious biases, and even to the point of changing their minds occasionally. If they weren’t, power would not shift so easily between political parties due to dissatisfaction of the electorate with their leaders.

Populations tend to follow a normal distribution for about any trait you can measure. There’s no reason this would not be true for the magnitude of the tendency to reinforce biases dividing in-group and out-group. On one end of the scale are those derided (by people on the opposite end of the scale) as “bleeding-heart liberals” - by definition they have more empathy than average for people in out-groups.

The opposite of the bleeding-heart liberal is someone who is more hostile to out-groups than average. But the opposites are not perfectly balanced, because a tendency in this group is easily reinforced by fear-mongering, which appeals to the unconscious limbic system. Indeed, Ito et al. (1998) presented evidence that we react much more strongly to a negative stimulus than a positive one. This makes sense given that fear, stress and the like activate the sympathetic part of the autonomic nervous system, which among other responses, increases adrenaline as part of the well-known “fight-or-flight” response. The parasymathetic response is simply the absence of of the sympathetic response; there is no equivalent effect that positive stimuli have on the body, and the mind.

This all means that arguments appealing to reason are paradoxically less compelling, because they require a conscious effort by the listener to respond in rational manner. Arguments based on fear work better in general because they appeal to our unconscious, requiring no intellectual investment on the part of the listener.

The “hostile” end of the in-groups vs. out-groups spectrum would be less able to overcome these unconscious tendencies with conscious reason. This is a possible explanation for hard-core right-wing pro-Bush Americans holding steady at a polled 20% of the population, despite what the majority of the population sees as a disasterously failed presidency. One might hypothesize that fear has a greater effect on the opinions of this 20% than on other people. Their social and political views are colored to a greater extent by emotion than those of other people, who are better at using their conscious mind to overcome instinctive biases; thus the use of political “code-words” that appeal to their baser natures.

Of course the 20% believe they have rationally thought out their views, because the emotional appeal of fear and divisiveness occurs at an unconscious level. The opposite 20% who prefer to love all mankind do not have an equally negative impact on society, because their views promote peace rather than conflict.

So Dick Cheney will always have the ear of people for whom fear drives political opinion; clearly he is one of them himself. It is much harder task for a president appealing to rationality to persuade. The main advantage to Obama right now is that the blatant politics of fear of the last eight years have been abysmally unsuccessful to the point that most of those who were swept up in it post-9/11 have now asserted conscious control over baser instincts that they now recognize to be destructive to society in general. But not all of them, thanks to the bell curve.

References

Ashburn-Nardo, L., Voils, C.I., and Monteith, M.J., 2001. Implicit associations as the seeds of intergroup bias: How easily do they take root? Journal of Personality and Social Psychology 81(5)789-799. 0022-3514/01/S5.00 DOI: 10.1037//0022-3514.81.5.789

Ito, T.A., Larsen, J.T., Smith, N.K. and Cacioppo, J.T., 1998. Negative information weighs more heavily on the brain: the negativity bias in evaluative categorizations. Journal of Personality and Social Psychology 75(4):887-900.

Tobena , A. Marks, I. Dar, R. 1999. Advantages of bias and prejudice: An exploration of their neurocognitive templates. Neuroscience and Biobehavioral Reviews 23:1047-1058.