Lourdes save me!: "Hankering after the lie"

Emile Zola's emotionally powerful book, Lourdes, published in 1894, is a poignantly detailed account of people suffering from severe disease, traveling to Lourdes, France, in the hopes of a miracle cure at the hands of a young maid, Bernadette Soubirous.  It was her visions, years earlier, that started the phenomenon by which the Virgin Mary was supposed to have endowed the local waters with miraculous healing properties.  Zola spent some time at Lourdes, to soak himself in the phenomenon and live up to his idea of 'naturalism', making the novel a kind of fictionalized documentary.

Bernadette Soubirous (source: Wikipedia)

Bernadette's story turned the Grotto at Lourdes into a major pilgrimage destination for those most in agony.  They crowded together in trainloads by the tens of thousands, rumbling across France to Lourdes in the hope of a cure centered around the intervention of God, prayer, priests, or angels. In his sympathetic empathy for people "hankering after the lie" of a miracle just down the track, Zola was understanding, but his explicit, highly angry skepticism was made, one might say, painfully clear.

Zola's tale is full of the wrenching tears, sadness and suffering of people with the most desperate of problems that medicine couldn't cure.  Indeed, this is as most of us will be when our time finally comes.  Most of humanity have died not knowing that their hoped-for miracles never happened. Today there are still desperate or credulous people who seek cures from God or from mountebanks, but at least those who are reasonably educated and have the access mainly trust to empirical medical science; that seems a huge conceptual jump beyond simple, desperate prayers.  Medical science is a huge conceptual jump beyond simple, desperate prayers, and has marvelously transformed our health experience, especially in the developed world. We have to be entirely thankful to the biomedical research and clinical systems for this.  Who would trade our medical (or dental) lives for those of the 19th century?  Still, I'll wonder below whether there's some potential irony in that.

Flooding to miracle waters by the trainload.  Source: Wikipedia

"The need of the Lie, that necessity for credulity, which is characteristic of human nature."
A young woman, Marie, a suffering heroine in Lourdes, had become paralyzed in an accident. She poignantly believes in St Bernadette,  and says glowingly after hours of intense prayers at Lourdes that "At four o'clock I shall be cured!"  And she was--but it was no miracle, as we'll see.

Zola noted in great and angry detail how the simple purity of Bernadette in her (apparent) apparitions and belief in the curative powers of the waters, were quickly shunted aside, and co-opted as a grotesque source of mammon by Church officials, turning Lourdes into a kind of health-tourist Disneyland: "An elaborate organisation had been gradually perfected, donations of considerable amounts were collected in all parts of the world, sufferers were enrolled in every parish...."  Do we not have our equivalent in much of the biomedical system today?  Research clearly is costly, but one must note the similar self-serving and open-ended nature of this enterprise side of things, engaged in by our particular version of the high priests, the academic 'church', and the magical waters it promises in our own time.  This is actually not new, even to medicine, and the various territory-guarding priesthoods of health go back to Hippocrates.

One could perhaps, write a similar novel today.  Patients wouldn't be in crowded trains but in crowded waiting rooms in hospitals, or in the skilled nursing sections of a modern retirement center. The struggle to get 'hospitalisation' care in Zola's time, or tickets on the trains to the curative waters of Lourdes, is today the struggle to get care covered by insurance, or to get a bed or scheduled treatment.  It might seem more orderly, and be administered by bureaucrats rather than nuns and priests, though as Zola clearly documents, the Church was a massive bureaucracy of its own, even when it comes to formal committees--including at Lourdes--to give the imprimatur to claims of miracle (not so unlike today's PR empires trumpeting each daily research miracle?).  The psychological and even material circumstances are quite similar, because the old pathos and wishful thinking are still here, along with the hopes, dreams and judgments, though perhaps they're often harder to see as people sit quietly waiting for the nurse to call their names.

Ironic cautionary notes?
Zola rants at length against a world driven by superstition and false hopes, exploited by religions.  He pleads for a new religion, one based on reason, as he calls it, that is about the realities of finite life and its imperfections, rather than imaginary wishful-thinking.  But there is an irony in his emotional plea, one we might listen to carefully: he notes that this superstition still existed after what, even then, had been a century of science with its touted powers and promises.  The failure of science to cure their diseases was leading people to return to superstition, rejecting science--rejecting reason.

Zola bemoaned that the "thirst for the Divine, which nothing had quenched....seemed to have returned with increased violence at the close of our century of science....it seemed that science alone cold not suffice, and one would be obliged to leave a door open on the Mysterious....what divine falsehood...could be made to germinate in the contemporary world, ravaged as it had been upon all sides, broken up by a century of science?  Ah! unhappy mankind, poor ailing humanity, hungering for illusion, and in the weariness of this waning century distracted and sore from having too greedily acquired science, it fancies itself abandoned by the physicians of both the mind and the body, and, in great danger of succumbing to incurable disease, retraces its steps and asks the miracle of its cure of the mystical Lourdes of a past forever dead!"

We've now had an additional century of science since Zola's book was published.  That we still have unconquered disease is understandable.  Diseases are diverse, and those we still cannot cure or prevent present massive challenges.  Of course, the target is an ever-moving one, with solved problems giving way to the unsolved ones that remain.  For the latter, even highly touted new treatments often only help some patients and it is not at all unusual to see that highly hyped new treatments in reality add but a few months of life, or a partial remission, for but a fraction of those who received them--and it is not necessarily true that those extra months are all that tolerable.  We are aided and abetted in the strong claims by the media, university or commercial spinners, and the interlocked careerist, funding-based mutually reinforcing systems.  So far, in our century, the public is buying it, as ever.

No fault lies in our not having divined (forgive the metaphor!) a cure, and the exaggerated promises of transformative advances are understandable in human terms--but not so different than what was coming from other pulpits in times past.  Is there any danger that the public will again see science, with its opulent cathedrals and assertive promises that often mammonize hope, as an enterprise of false illusions?  The suffering remain, after all, in the realm of fear, not reason.  To what alternative solution--or lie--might their hopes turn?

Of course, our inherent inevitable mortality means even our modern system will ultimately fail every one of us. As sentient organisms we don't want pain, and as knowing organisms we don't want death, and it is all too easy to 'Tsk, tsk' the system when it is others than ourselves suffering from awful diseases, and it's not yet our turn.  Ultimate failure is an open secret that neither the system nor its patients like to acknowledge.  The currently growing hospice movement is facing these realities, unless it too becomes co-opted as a 'system' with its own self-interested self-promotion.  Precedent suggests that may happen, but it's a very good thing at present, as we've noted here before.

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Zola visiting Lourdes.  Wikipedia, from the magazine Gil Blas, 1894

Maybe some day we'll have the promised cures, sipping genetics or whatever other magic waters come along.  If so, then the medical priests will have earned their respect in every way.  But of course that, too, is a dream.  If all known diseases were cured by one miracle or another, we would still degenerate or even if that could be prevented, we'd be so numerous as to be stacked many-high on top of each other, struggling for food or water and so on--a geriatric nightmare of its own sort.

An ironical year
A century on from Zola's time we may still be at risk of people again turning away from the exaggerated promises of science, and given much of the world today it would be ironic but not so strange if there were a turn to some form of religion or mysticism, some emotional rejection of 'objective' science.  

But there is another sort of irony in the story of Lourdes.  In 1858, eerily reflecting the impending conceptual clash that Zola writes of, while the real Bernadette Soubirous was having the visions that would lead to the pilgrimages to the waters of Lourdes, Charles Darwin and Alfred Wallace publicly announced their discovery of evolution, that directly threatened religious explanations and led steadily to the altars of science instead as a competing explanation for human affairs. 

Zola's touching kind of docudrama makes one aware of the nature of hope, as well as false hope, and our willingness to believe what our particular day's preachers promise.  Zola himself bitterly debunks the claims at Lourdes.  Many of the pilgrims died, some reported improvement (almost always temporary), and only a few were 'cured'.  The trains left somewhat emptier than they were a few days earlier, populated by the returning survivors, still with their ailments, each inspired that the cure will surely happen to them at Lourdes next year!

As described in the link given below, a biography of Zola suggests that he saw a cured case of tuberculosis but changed that to a fatality in his book, to make his main point against superstition. But he was very clear that, as we often see reports today of, for example, placebo effects, it was nervous afflictions (that we refer to by terms like 'psychosomatic') that seemed most likely to be 'cured'.  Real physical problems were not.  The hero in Zola's book, a doubting priest who even had carnal feelings for Marie, understood that that was the nature of her 'cure', but in deference to her faith in Bernadette he made the altruistic decision to let Marie live with her illusions, thus permanently distancing her from his non-belief.

Such a book, though sometimes a bit ponderous in realistic details, is a good reminder of the human rather than just the sociopolitical, economic or even coldly scientific sides of the story.  But this should not take our eye off the importance of keeping science's eye on the proper ball: not that of self-serving empire building and inertia, but of truly addressing human agonies in the best way possible, fallible though we be.

Overall, perhaps we never learn--or, maybe, in being mortal it is not possible that we can learn, and completely accept the grim-reaper's realities that we know, in our hearts, are there.  At least, each of us will have to learn this in his or her own way, at the end.  No miracle can prevent that.

An afternote for fiction lovers
Here is a very nice blog post discussing Lourdes.  The blog is a fine one, about great literature that has survived fads and fashions and stands on its own legs.

Heart disease - the 7.5% solution?

Statins are in the news again, and not just because of the new PCSK9-based drugs, at least one of which is likely to be approved by the FDA this week, probably for a small class of at-risk patients.  These drugs will drive LDL cholesterol levels through the floor, while generating an estimated 17.8 billion for pharma by the year 2023 (and that's before we even know whether they will reduce risk of heart attack and stroke).

No, this is about your run-of-the-mill class of LDL-lowering statins.  In late 2013, the American Heart Association and the American College of Cardiology recommended new guidelines for determining who should be on statins.

• anyone who has cardiovascular disease, including angina (chest pain with exercise or stress), a previous heart attack or stroke, or other related conditions

• anyone with a very high level of harmful LDL cholesterol (generally an LDL above greater than 190 milligrams per deciliter of blood [mg/dL])

• anyone with diabetes between the ages of 40 and 75 years

• anyone with a greater than 7.5% chance of having a heart attack or stroke or developing other form of cardiovascular disease in the next 10 years.

Risk score is based on the ASCVD calculator, which uses basic data (age, sex, total cholesterol, HDL cholesterol, systolic blood pressure, and smoking and diabetes status) to calculate risk.  Unlike the previous Adult Treatment Panel III (ATP III) guidelines which were based on a target LDL level and risk factors determined by the long-term Framingham heart disease study (using the Framingham Risk Calculator), these new guidelines were based on a risk profile.  With these new guidelines, it was thought that about 13 million additional Americans would benefit from statins, for a total of a third of all Americans.

A study published in the Journal of the American Medical Association last week asks whether these guidelines were better at identifying at-risk individuals than the old ATP III guidelines.  The prospective study followed up 2435 people from the Framingham study who had never taken statins.  Based on the ATP III guidelines, 14% would have been 'eligible' compared with 39%, based on the 2013 guidelines.

The median follow-up was 9.4 (interquartile range, 8.1-10.1) years. There were a total of 74 (3.0%) incident CVD events (40 nonfatal myocardial infarctions, 31 nonfatal strokes, and 3 with fatal CHD) and 43 (1.8%) incident CHD events (40 nonfatal myocardial infarctions and 3 with fatal CHD).

Among those eligible for statin treatment by the ATP III guidelines, 6.9% (24/348) developed incident CVD compared with 2.4% (50/2087) among noneligible participants (HR, 3.1; 95% CI, 1.9-5.0; P less than .001). Applying the ACC/AHA guidelines, among those eligible for statin treatment, 6.3% (59/941) developed incident CVD compared with only 1.0% (15/1494) among those not eligible (HR, 6.8; 95% CI, 3.8-11.9; P less than .001). Therefore, the HR of having incident CVD among statin-eligible vs noneligible participants was significantly higher when applying the ACC/AHA guidelines’ statin eligibility criteria compared with the ATP III guidelines (P less than .001).

That is, according to this study, the 2013 ACC/AHA guidelines identified more people at risk of heart disease than the ATP III guidelines.  That's presumably progress in understanding heart disease risk, and so a good thing. (Does anyone else find the use of the word 'eligible' odd, though?  Like statins are a reward for passing the risk threshold?)

But why don't they ask about family history?  That is one of the most useful bits of data a physician can have about a patient's risk of heart disease (and other things).  Is it too cynical to suggest that acknowledging its usefulness might diminish the importance of what has been learned from the Framingham study?

Less cynically, one reason, though we don't know if the various investigators considered it in this way, is that family history integrates all factors, including those that are being specifically measured (like blood pressure, LDL levels, and so on). Whether they are genetic or environmental, they went into determining whether the relative had heart disease.  So counting family history and LDL, or for that matter, weight and BMI, also not included, may be redundant to an unknown extent.  For risk factors, this would perhaps inflate the apparent risk, but for protective factors the opposite.  But family history is debatably the best single factor, perhaps as important as all the test-battery factors.  At least, it's important to consider why that alone, or that somehow corrected for redundancy, should be a part of all of this.

So, apparently we don't know more about the causes of ASCVD now than we did before 2013, we're just evaluating what we know differently.  So, assuming that statins really do reduce risk of ASCVD, that more people are 'eligible' is thought to be a good thing.  Though, as the JAMA commentary on this article notes in urging increased treatment with statins, "Although a 10-year ASCVD risk threshold of 7.5% or higher might initially seem to be a low threshold, many, indeed most, CVD events occur among the low-risk members of the population."

Wait!  "Low-risk" is defined by us, based on what we know about heart disease!  Our understanding is clearly wrong if all these 'low-risk' people are really high-risk!  Not to mention that there's clearly a huge false-positive pool if a risk estimate of 7.5 out of 100 makes a person eligible for statins!  That means that 92.5 of those 100 people are taking statins even though they weren't going to have a stroke or heart attack.  And, all this means, at least to me, that we really don't understand what causes heart attacks or stroke. The Framingham study identified cholesterol, particularly LDL, as a risk factor, but we're not really sure why, and we don't know what levels are in fact most risky, and people with low LDL can have heart attacks, too.  Statins may or may not work by reducing LDL cholesterol, and lower LDL cholesterol may or may not reduce risk.

And, statins can have serious side effects -- physical as well as the cost burden.  So, if of 100 people taking statins a large majority weren't going to have heart attacks anyway, statins are causing a lot of unnecessary side effects without preventing disease.  Though, to be fair, physicians can't predict the future, and must do their best with the information they have.  They don't know who will or won't have a heart attack, because epidemiology hasn't given them enough information.  They've got to treat people with 7.5% risk as if they are at 100% risk of disease.

So, it's not physicians who are failing here, it's epidemiologists.  But I'll even be fair to epidemiologists -- it's the methods, based on population data and probability (which may not even exist; see our series of posts on this starting here), that are failing.  Epidemiologists are doing their best with what they've got.  We don't know precisely what causes heart attacks, but to prevent them, we've got to treat people with low risk as though they are at high risk, and that's because some people at low risk really are at high risk.

No one has 7.5% of a heart attack.  They have 0% or 100% of a heart attack. Figuring out who is in which group is currently impossible.  What we do know for certain is that putting everyone on statins, as though they have 100% risk is very good for the pharmaceutical companies that make them, and good for people whose heart attack or stroke was prevented, even if we will never know which people these were, and unnecessary and even harmful for everyone else.

This is a lousy way to do medicine.  But it's currently the only way we've got.

'Obstetric dilemma' skeptic has c-section and remains skeptical ... & ... Why my c-section was natural childbirth

This is a new kind of Tale for me. The rock'n'roll's turned way up, and every couple sentences I have to stop typing to twirl a blue hound dog, a bear holding an umbrella, a Flying Spaghetti Monster, and other oddities that I strung up to hypnotize this little guy into letting me type one thought at a time:

The thing that needs to be hypnotized.
Or the three wise monkeys say: The thing that makes it impossible to create or to dwell on the negative. (e.g. his birth by c-section)

That young primate's the reason I've been quiet for a while here on the MT. And he's the reason I'm a bit more emotional and I cry harder than usual at Rise of the Planet of the Apes (those poor apes!), Cujo (that poor dog!), and other tearjerkers. But he's also the reason my new favorite animal is plain old, fascinating, and dropdead adorable Homo sapiens.

In anthropological terms, he's the reason I'm overwhelmed, not just in love but in new thinking and new questions about the evolution of human life history and reproduction, and then what culture's got to do with it and with our reconstruction of it.

Some context would help, probably.

For the past few years I've been challenging the 'obstetric dilemma' hypothesis--the idea that hominin mothers' bipedal pelves have shortened our species' gestation length and caused infant helplessness, and that antagonistic selection between big-brained babies and constrained bipedal mothers' pelves explains childbirth difficulty too.

[For background see here or here or here or here.]

As part of all that, I've been arguing that the historically recent surge of c-sections and our misguided assumptions about childbirth difficulty and mortality have muddled our thinking about human evolution.

So, once I was pregnant, you might imagine how anxious I was to experience labor and childbirth for myself, to feel what the onset of labor was like, and to feel that notorious "crunch" that is our species's particular brand of childbirth. Luckily I was not anxious about much else the future might hold because modern medicine, paid for by my ample health insurance, would always be there to make it all okay. After a long pregnancy that I didn't enjoy (and am astonished by people who do) I was very much looking forward to experiencing childbirth. In the end, however, my labor was induced and I had a bleeping c-section.

But my bleeping c-section's only worth cussing over for academic reasons because the outcome has been marvelous, and the experience itself was out of this world.

We'll get to the reasons for my c-section in a second, but before that, here are the not-reasons...

First of all, I did not have a c-section because I fell out of a tree with a full bladder.

Second of all, shut your mouth... a c-section was not inevitable because of my hips.

Okay, you got me. I've never been even remotely described as built for babymaking. My hips are only eye-catching in their asymmetry. One side flares out. It might be because when I was 15 years old I walked bent-kneed for a few months pre- and post-ACL reconstruction. That leg's iliac crest may have formed differently under those abnormal forces because, at 15, it probably wasn't fused and done growing yet. If you like thinking in paleoanthropological terms like I do, then my left side is so Lucy.

Anyway. I'm not wide-hipped. However, guess how many nurses, doctors, or midwives who were involved in our baby's birth think my pelvis was a note-worthy factor in my c-section? Not one.

Hips do lie! Inside mine there's plenty of room to birth a large baby. Two independent pelvic exams from different midwives (who knew nothing of my research interests at the time) told me so, and it sounded like routine news to boot. Although one midwife asked me "do you wear size nine and a half shoes?" (no, I wear 8) which was her way of saying, "Girl, you're running a big-and-tall business. You got this."

What you probably know from being alive and knowing other people who were also born and who are alive (or what you might hear if you ask a health professional in the childbirth biz) is that most women are able to birth babies vaginally, even larger-than-average babies. And that goes for most women who have ever lived. Today, "most women" includes many who have c-sections because not all c-sections are performed because of tight fit between mother's birth canal and baby's size. As I understand it, once the kid's started down into the birth canal and gets stuck, a c-section's no longer in the cards. So performing c-sections for tight fit is a preventative measure based on a probability, not a reflection of an actual tight fit. In the mid 20th century, tight fit used to be estimated by x-raying pregnant women and their fetuses. Can you imagine? And this was right about the time the obstetric dilemma hypothesis was born. I don't think that's a coincidence.

Here's a list of reasons for c-sections. Tight fit is included in the first bullet point. Tight fit is one of the few quantifiable childbirth risks. No wonder it's so prominent in our minds. That list excludes "elective" ones which can be done, at least in Rhode Island, if they check the box that says "fear of childbirth". And that's not even close to a list of reasons why women around the world and throughout history have died during or as a result of childbirth. For example, about a hundred years ago women were dying all over the place because of childbed fever.

Anyway, we should assume that I am like most women and expect that I could have given birth the way Mother Nature intended: through my birth canal and with the participation of other humans. Oh yeah, when it comes to humans, social behavior and received knowledge are part of natural childbirth. Even this natural childbirth (which has inspired a forthcoming reality television show featuring women giving birth in the wild!) involves the supportive and beneficial presence of other humans as well as the culture that the mother brings to the experience.

But a c-section's just culture too, so could it be part of "natural" childbirth, then?

I'm inclined to blurt out yes, of course! because I don't support calling anything that humans do "unnatural." But I know that's not something everyone agrees with. It's politics. For example, many of you out there don't flinch an inch at the subtitle of Elizabeth Kolbert's book, "The Sixth Extinction: An Unnatural History."  And given the present energetic movement against childbirth interventions, describing c-sections as "unnatural" as climate change could help minimize unnecessary ones for those who wish to give birth vaginally.

So there we have it. These are the two enormous issues raised by my own little c-section: What can it teach us about the evolution of gestation length, infant helplessness, and childbirth difficulty? And could it be considered natural?

One way for me to get at these questions is to try to understand why I experienced "unnatural" childbirth in the first place. So here goes.

Here's why I think I had to have a c-section:

1. My pregnancy ran into overtime.

This is expected for nulliparous mothers. I visited one of my OBs on my due date. He put his finger on the calendar on the Friday that was two weeks out and joked, "Here's when we all go to jail." Then he asked me, "Who do you want to deliver your baby? I'll see when they're on call before that Friday and schedule your induction then." And I chose my favorite midwife and he scheduled the induction.

All right so I was running late compared to most women, but that's still natural, normal. But it also means risks are ever-increasing by the day. And no matter how small, that the professionals know how to mitigate the biggest risks of all, *deaths*, means that they try to do that. They're on alert already as it is, and then they're even moreso on edge when you're overdue. Especially when it's your first baby and you're a geezer, over 35 years of age.

Now, does going overdue mean the baby keeps growing? Maybe, but not necessarily and not necessarily substantially. Both of us, together, should have been reaching our maximum, metabolically. There's only so much growing a fetus can do inside a mother.

When I approached my due date, and then once I went past it, I tried to eat fewer sweets to make it less comfortable in my womb. I also went back to taking long, hard walks, five milers, even though it was hard on my bladder because I thought that might help kick him out too. I even ran the last of my five miles the day before my induction, to no avail other than the mood boost it gave me.

2. I didn't go into labor naturally by my due date or by my induction date 11 days later. 

Although my cervix was ripening, when I went in to be induced I was only dilated 0-1 cm. I had 9+ more to go before the kid could get out at 10. So a balloon catheter was inserted and filled with water, and I had to tug on the tail of it, which tugged the balloon, which put pressure on the cervix. It dilated enough that it fell out several hours into the process, and by morning I was dilated 3-4 cm. This was exactly the goal of the catheter, this many centimeters. All was going well. However, that the cervix did not open on its own is already a missing piece of going "natural," of having my own biology contribute to my childbirth experience. So starting this way is already derailing things, making it difficult for anything natural to follow, naturally.

3. The fetus's head was facing the hard way: sunnyside up.

This was assessed by the midwife and cradling my belly in a bedsheet, with me on all fours, she and I could not twist him into a better position. His head, she said, was probably why I did not dilate naturally. When I asked an OB during my postpartum check-up, "What dilates the cervix?", he said "We don't know. But I can tell you it's not with the head like it's a battering ram." Well, then... hmph. And then I asked him if women carrying breech fetuses have trouble dilating their cervixes, or going into labor naturally, and he said not necessarily. No. Hmph.

Regardless of what causes cervical dilation, if the head isn't facing the right direction, it's notoriously tough to get down into the birth canal, let alone through the birth canal. It's not impossible, not even close. But it's not looking good at this point either. Perhaps the contractions will jossle his head into a better position, they said. And the contractions should further dilate the cervix.

4. Contractions didn't get underway, naturally, after the catheter dilation, so the drug pitocin was used. 

Induction and pitocin increase the chances that a mother will ask for drugs to help with pain and that she will have interventions, like a c-section. See for example this paper. What the causes are, I'm not sure. But pointing out the correlation is useful at this point because at this point, without even getting into hard labor yet, and without finding out whether my cervix does its job, I'm more likely than ever to be going to the operating room.

5. After six hours of easy labor and five hours of intense labor, my cervix never dilated past 5 cm.  

It needs to get to 10 cm to get the baby moving into the birth canal. Just like with due dates, I think that blanketly assigning this number to all women is probably not consistent with variable biology, but it's how it's currently done. And maybe any higher resolution, like "Sally's cervix needs to hit 9.7 cm", is pointless.

After several hours pitocin-induced contractions--which at first felt like the no-big-deal Braxton-Hicks ones I'd been having numerous times daily for the whole third trimester--I only dilated 1 cm more. That's even when they upped the pitocin to make them more intense.

But after they saw I'd made essentially no progress and that I was napping to save my energy for when things got bad, they woke me up and broke my bag. It would be nice if they could have let my labor progress slowly, if that's what my body wanted to do, but remember, my personal biology went out the window as soon as induction began. And then when that amniotic fluid oozed out of me, that's when bleep got real.

Every two minutes and then every one and a half, I grabbed Kevin's extended hand and breathed like an angry buffalo humping a locomotive. It was the worst pain of my life and I was afraid I'd never last to 10 cm, so I took the stadol when I told the nurse my pain was now at a 9 out of 10 (all previous answers to this question were no higher than 2). I was going to avoid the epidural no matter what, even at this point, because I was more afraid of the needle sticking out of my spine for hours of labor than I was afraid of these contractions. I have no idea if the stadol dulled any pain, because the pain just got worse, but it did help psychologically because it put me to sleep between contractions. There was no waiting with anxiety for the next one and time flew by. But after five hours of this, I had not dilated any more. But I had vomited plenty! And although I'd fended off the acupuncture (FFS!), I folded weakly and, for the peace of mind of a wonderfully caring nurse, I allowed a volunteer to perform reiki on me. And what a tragedy it was! Wherever she is, there's a good chance she gave up trying to help laboring women, and she may have given up reiki all-together.

The hard labor story ends at five hours because that's about when the nurse actually screamed into the intercom for the doctor. My contractions were sending the fetus into distress.

6. After five hours of intense labor, the fetus was experiencing "distress" at every contraction, as interpreted from his heart-rate monitor. 

Basically, he was bottoming out to a scary heart-rate and only very slowly coming back to a healthy heart-rate just in time to get nailed by another contraction. By the way, this is the official reason listed in my medical records for my c-section: fetal distress.

I know that a heart-rate monitor on the fetus is another one of those medical practices that increases the chances of an "unnatural" childbirth. That's probably because all fetuses are distressed during labor, but observing the horror, and then guessing whether it's safe to let it continue is seemingly impossible. So at some point, like with me and my fetus, they get alarmed and then how do you back down from that?  They gave me an oxygen mask which immediately helped the fetus a bit, but like I said, hackles were already up at this point. Soon thereafter we had a talk with the doctor about how I  could go several more hours like this and get absolutely nowhere with my cervix, and then there are those life and death matters. She never said c-section. I had to eek out between contractions, "So are you saying we need to perform a c-section?" and she said yes, and urgently. A c-section sounded like the only solution at this point both to battered, old me, to clear-minded Kevin, and clearly to the delivery team (and in hindsight, it still does to Kevin and me). Then, lickety-split, the anaesthesiologist arrived, got acquainted with our situation, and made me vomit more. And then like a whirlwind, Kevin's putting on scrubs, and we're told to kiss, and I'm jokingly protesting "I'm a doctor too!" while being wheeled into the operating room because I cannot walk through my contractions.

It's bright white, just like Monty Python said it would be. I sat on the crucifix-shaped operating table to receive all the numbing and pain killing agents through my spine. Somehow they pulled this off while I was still having massive contractions. Then I laid down, arms splayed out to the side, and they drew a curtain across my chest, a nurse told me how creepy it was about to be, and they got to work.

Although the c-section wasn't painful, I could feel everything. This was my childbirth experience. I felt the incision as if she was simply running her finger across my belly, and I felt the tugging and the pressure lifting from my back as they extracted my baby from me. After that, and after I got a short glimpse of him dangly over my left arm--"He's beautiful! He's perfect! He's got a dimple! He growled!"--I continued to feel many things, probably the birth of my placenta, etc...

But I didn't know what exactly I was feeling until I watched a video of a c-section on YouTube. Kevin helped fill in the details too. He had caught a naughty glimpse of the afterbirth scene before being chased back to his designated OR spot with the baby. Thanks to him (and that video) I know now that I was feeling my enormous muscular uterus and some of my intestines being yanked completely out of a small hole right above my pubic bones and then stuffed back in. For a few moments, it must have looked like I was getting re-inseminated by a red octopus.

I tell everyone that it was like going to outer space to give birth. And this, if you know me, is an exciting idea so my eyes are smiling and I sound dreamy when I say "it was like going to outer space to give birth!" I bet you're thinking it's the Prometheus influence, but you'd have the wrong movie. The correct one is Enemy Mine. And it's much more than that, actually. I was as jaw-dropped and awe-struck by humanity during my childbirth experience as I am by space exploration. The orchestration, the specialization, the patience, the years of study, of planning, the calculations, the dexterity. To boldly go. Wow. Like I said, humans are my new favorite animal.

I was back in our little room quicker than most pizza deliveries, where our bright red new baby was trying hard to nurse from his daddy. Then he nursed from me. And the story's all mushy weepy cuddly stuff from now on. So let's not. Let's remember what we're here for. Okay. Right.

7. The cord was wrapped twice around his neck. 

We found this out when he was cut out of me. That didn't help with moving him around in utero to a good position, nor did it help with oxygen flow during contractions! This would not have inhibited his safe vaginal birth, however, at least not necessarily.

8. He was enormous. His head was enormous too. 

He came out a whopping 9 pounds, 13 ounces, 22.25 inches long, with a head circumference of 15.5 inches. They say that's heavier than he'd be if born vaginally because he didn't get all the fluids squeezed out of him. But still, that's large. According to the CDC he was born as heavy as an average 3.5 month-old boy. His head was about the size of an average 2.5 month-old.

Red line is our baby's head circumference at birth. (source)

Way back at the mid-pregnancy ultra-sound, we knew he was going to be something. And then if you'd seen me by the end, like on my due date, you might have guessed I was carrying twins. I was so big that my mom joked she thought maybe a second fetus was hiding behind the other one, undetected.

Smiling on my due date because pregnancy was almost over. 
(By the way, I could still jog and I dressed weird while my body was weird.)

If I hadn't had the means to eat so much like I did during pregnancy, perhaps he wouldn't have grown so large inside me. If I hadn't lived such a relaxed lifestyle while pregnant, maybe he wouldn't have grown so large inside me. If I didn't have a medical safety net waiting for us at the end, perhaps I would have been scared into curbing my appetite from the get go. I gained 40 pounds. With this body, but in a different life, a different place, a different time, maybe I wouldn't have. Probably I wouldn't have.

His size has got to have influenced a few of those other contributors to my c-section. But clearly it's more complicated than his size. And this brings us back to the obstetric dilemma. Let's say he was too big or that his large size screwed everything up, even if he could technically fit through the birth canal. Well then, why didn't I go into labor? Labor triggers are, to me, a significant problem when it comes to explaining the evolution of gestation length in humans, and whether we have a unique problem at the end.

If our pregnancy length is determined by available energy, energy use, and metabolism (here and here) then women like me who go overdue, who are clearly not killing our babies inside us either, are just ... able to do that. But doing that clearly leads to problems in our species (one of the few known) that has such a tight fit to begin with.

If our pregnancy length is determined by our birth canal size, and any anatomical correlates, then why didn't I go into labor before my fetus got so big? What went wrong? What's frustrating too is, for my n of 1, we'll never know if I could have given birth vaginally because I never got the chance to try.

These seem like simple questions but they are deceptively complex. And I think there will be some exciting discoveries to come from medicine and anthropology in the coming decades to explain just how our reproduction works which will in turn help us reconstruct how it evolved.

What's my birth experience got to do with evolution? Why, everything. It's got everything to do with evolution, because if it's not evolution, it's magic.  And that's kind of where I'm coming from when I say that my c-section was still natural childbirth. It wasn't unnatural and it certainly wasn't supernatural. Sure, it's politics. I'm invested in the perspective that humans are part of the evolving, natural world and want others to see it that way or, simply, to understand how so many of us see it that way. But it's not just evolution that's got me enveloping culture into nature and that's got me all soft on the folks who drive fancy cars who cut my baby out of me.

Who knows what could have happened to my son or to me if we didn't have these people who know how to minimize the chances of our death? It's absolutely human to accumulate knowledge, like my nurses, midwives and doctors have about childbirth. Once learned, it's difficult for that knowledge to be unseen, unheard, unspoken, unknown. Why should we expect them to throw all that away so that we can experience some form of human being prior to that knowledge?

Nature vs. Culture? That's the wrong battle.
What matters is which one can fight hardest on my behalf against the unthinkable.

Maybe childbirth is so difficult because it can be. We've got all this culture to help out when things get dicey, with or without surgeons. On that note, maybe babies are so helpless because they can be. We've got all the anatomy and cognition to care for them and although the experiment would be impossible, it's doubtful any other species but ours could keep a human baby alive for very long. It could just be our dexterous hands and arms, but it could be so much more, like awareness of their vulnerability and their mortality,and (my favorite pet idea) awareness that they're related to us. Culture births and keeps human children alive with or without obstetricians. It's in our nature. Maybe it's time we let all this culture, our fundamental nature, extend into the operating room.

Lunch with the Captain

These days I’m having trouble finding time to write, especially to blog.

My colleagues and I are busy building a team and a large network of collaborators for a series of related malaria elimination projects.  Our initial goal in this project is to wipe malaria out in very specific populations.  If this works, and from our initial work at a smaller scale it appears as though it can, it will be vastly scaled up – reaching throughout Southeast Asia.

The impetus for this work is the so-called evolutionary arms race.  This part of the world has a very long history of popping out drug and multi-drug resistant strains of falciparum malaria (C Wongsrichanalai et al., 2001; Chansuda Wongsrichanalai, Pickard, Wernsdorfer, & Meshnick, 2002).  We (malaria workers) roll out a new line of defense (antimalarials) against our chosen adversary, and our adversary quickly develops a defense strategy against us.  These strains can subsequently move from this part of the world to others, parts of sub-Saharan Africa for example, where the malaria burden is much heavier and the results would be much more devastating (Payne, 1987).

Occasionally there are deaths from malaria infections here along the Thailand-Myanmar border (though usually the major toll the illness takes here is in time spent ill and therefore unable to work.)  Not that long ago, a 15 year old boy died from malaria.  He was not far from health care clinics that would have treated him.  The story I hear is that he was without close family members, he lived alone and worked in the agricultural fields, and that he essentially lay in those fields dying from the disease through an apparent gap in his and his community’s social network.  Everyone was devastated.  If complete drug resistance were to reach Africa, this story would be magnified in both space and time.  Even where the social networks were strong, the health clinics wouldn’t be able to adequately treat people with malaria.  The geographic reach would be huge and the numbers of death would likely dramatically increase.  This can’t happen.

Today our last, best tool against malaria is artemisinin and its derivatives.  But already throughout Southeast Asia researchers and health care workers are seeing parasites survive much longer in the human hosts after being treated with artemisinin (Ashley et al., 2014).  How much longer will it work at all?  And should we really wait to find out?  It often feels as though everyone around here has been doing the same “malaria control” game for a very long period of time, regardless of the fact that the outcome is always the same.  Our drugs stop working and we have to start over again.  Sometimes this problem is exacerbated by a lack of information and/or the dissemination of scientific knowledge.  Many of my Thai colleagues who actually work in direct malaria care in this area just learned last year (2013) that resistance to artemisinins might be occurring or even growing and spreading in their region.  A major scientific paper on this (that I’m aware of) came out 5 years ago (Dondorp, Nosten, & Yi, 2009), with rumors of it almost 10 years ago (Noedl et al., 2008)!  Shouldn’t the people who live in the war zone know that a war is happening!?  What a failure of science – and of our strategy over the long term.  It is time for a change.

So what we’re working on is a tool that we’re calling “targeted chemo-elimination.”  Essentially this is a form of mass drug administration.  That is, everyone in a targeted community would take drugs (antimalarials) regardless of whether or not they felt sick (some recent thoughts on this here, here, and here).  It is much more complicated than this though, in that it isn’t a single strong dose of the antimalarials, we’ll be using a cocktail of drugs so that we can hope to avoid further driving resistance, and since the administration will occur over time, over several stages, we’ll be able to vary this cocktail if necessary.

Logistically this is extremely difficult to pull off.  It is hard enough to get people in easy to reach populations in places like the U.S. to take medicine when they feel sick, let alone to take a vaccine that would prevent them from being sick.  How do we go about convincing people in extremely remote populations, frequently in the middle of old or continuing conflict zones, to take medicine, over a long period of time, regardless of whether or not they are currently feeling sick?  It isn’t easy.

But it can be done and the way to do it is through community engagement – drawing on notions and principles well-known in anthropology and other social sciences.  It can happen when there is understanding, trust, and social cohesion.  Sometimes these things are lacking in our target communities between members of the community, and/or between us and members of the community, and it is therefore important to build them up.  Sometimes we need to plant a seed, water it, foster it, and help it to grow.

This is exhausting work, physically, psychologically, and emotionally.

A little while back I made a trip to one of the communities in our target area, to visit local people and share some of what our project is about.  I wound up eating lunch at a table full of “freedom fighters”, some dressed in fatigues and drinking whisky out of small coffee cups.  A captain who was sitting at the table gave me a history lesson, translated to English through one of my colleagues who speaks both my tongue and the local language.  I heard stories about being betrayed by colonialists who promised these people their own land but never followed through and of people who were willing to die for that land, many of whom did in fact pay that price.

Among the things he said to me was that he admired two major things about Americans.  One is that their time is their money (time is extremely valuable).  And the other is that they realize they have a burden, to help others, that is bigger than a mountain (we were sitting at the base of a relatively large one).

I don’t know if this generalization is true of all Americans and I don’t care to go into that.  But I do know that time is of the essence and that I feel a burden.  There is a lot of work to do, and not so much time in which to do it.

*** As always, my opinions are my own.  This post and my opinions do not necessarily reflect those of Shoklo Malaria Research Unit, Mahidol Oxford Tropical Medicine Research Unit, or the Wellcome Trust. 

Ashley, E. a., Dhorda, M., Fairhurst, R. M., Amaratunga, C., Lim, P., Suon, S., … White, N. J. (2014). Spread of Artemisinin Resistance in Plasmodium falciparum Malaria. New England Journal of Medicine, 371(5), 411–423. doi:10.1056/NEJMoa1314981

Dondorp, A., Nosten, F., & Yi, P. (2009). Artemisinin resistance in Plasmodium falciparum malaria. The New England Journal of MedicineEngland Journal of …, 455–467. Retrieved from http://www.nejm.org/doi/full/10.1056/nejmoa0808859

Noedl, H., Se, Y., Schaecher, K., Smith, B., Socheat, D., & Fukuda, M. (2008). Evidence of artemisinin-resistant malaria in western Cambodia. N Engl J Med, 359(24), 2619–2620.

Payne, D. (1987). Spread of chloroquine resistance in Plasmodium falciparum. Parasitology Today (Personal Ed.), 3(8), 241–6. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/15463062

Wongsrichanalai, C., Pickard, A. L., Wernsdorfer, W. H., & Meshnick, S. R. (2002). Epidemiology of drug-resistant malaria. Lancet Infectious Diseases, 2, 209–218.

Wongsrichanalai, C., Sirichaisinthop, J., Karwacki, J. J., Congpuong, K., Miller, R. S., Pang, L., & Thimasarn, K. (2001). Drug resistant malaria on the Thai-Myanmar and Thai-Cambodian borders. Southeast Asian J Trop Med Public Health, 32(1), 41–49.

Homeopathic beer is totally watered down

Take a beer.

Sorry for the dilution scare.

Make it a great one like La Fin du Monde.

Take away all the beer molecules by diluting it like crazy.

Leave the vibrations behind.

Drink that water and you should have all the healing effects of real beer without all the calories or addictive effects.

It sounds magical.

So if homeopathy really worked wouldn't somebody be selling homeopathic beer at Whole Foods by now?

Of course they would, but it doesn't work. You'd drink the "beer," not get a smidgen of relief from the human condition, and demand your money back. Diluteries all over the country would have to shut down before they knew what happened.

Then why do people still buy piles of homeopathic medicines?

Compared to beer, it's harder to gauge or track the effects of headache pills; if you take a pill for a headache, it's hard to tell if your headache was relieved by the pill or just by your own body over time.  Homeopathic meds can also provide relief as much as placebos can (which can be effective!). So homeopathic medicines for headaches will keep selling and will keep making the people richer who stock the shelves at Whole Foods with water pills.

Sadly, homeopathic beer would never work. Even though beer is just sweet sweet medicine.

Next time James Randi and friends stage an overdose party, maybe they should wash those pills down with some of it. Maybe they already do.

The Amazing Story of Holly Dunsworth and her Osteopathic Doctor

Recently I read a fascinating article on The Huffington Post called, “The Amazing Story of Charles Darwin and his Homeopathic Doctor.”

Quoted from the article:

"We may all have to thank the water cure and homeopathic treatment provided by Dr. Gully for Darwin’s survival."

and

"Lucky for all of humanity, Charles Darwin sought out a different type of medical care and experienced a profound improvement in his health."

This article is a summary of a more detailed article that was published in a medical journal published by Oxford University Press, called eCAM (which stands for “Evidence Based Complementary and Alternative Medicine"). Click here to see the article in its entirety.

I hope that you read either of these articles and then come back.

Welcome back!

Now, I don’t know a whole lot about homeopathy. But I do know a little about science and I also know a little about some of the stuff James Randi has done to debunk homeopathy. So…Psssst….let me let you in on a little secret:

Homeopathy is cow manure.

(Masculinize “cow” and lewdify “manure” to decode my intended sentiment.)

The author of the article is using Darwin’s fame and notoriety to lend legitimacy to homeopathy.

Everyone wants a piece of Darwin, especially this year.

The questions that haunt me after reading the article are probably the same that you have:

• In Darwin’s day, how much more effective was medicine than homeopathy? How scientific was medicine?

• Was Darwin’s use of homeopathy a rejection of science in favor of alternative treatments, or did he simply choose one pretty hopeless option over another?

• Was Darwin's plight so different from that of many people today?

I’m sure that there are historians of science and medicine who have answers for these questions (and please see the thoughtful comments in the Comments section below). But I do know the answer to the last one and it’s NO.

For example, people with eczema can suffer terribly, and there's no certain or easy cure. And this is why people are still drawn to alternative cures, either right off the bat, once they start showing symptoms, or after real science and medicine have failed to help them.

Desperation leads us all to search for solutions to relieve our pain and suffering. However, homeopathy is absolutely stark-raving ridiculous.

If you want to see the kind of discussions people who seek homeopathic cures are having, take a look at this mind-blowing back-and-forth about a little girl with eczema. Make sure to read what "passkey" writes.

It’s actually not that surprising that so many people are drawn to homeopathy, because finding real medicine isn’t always as easy as it sounds.

Recently I learned this lesson for myself.

I’m new to Chicago and so every time I need a new doctor I have to find one. So I go to my insurance company’s website and search for doctors in my neighborhood who do what I think I need them to do based on their listed area of expertise.

I had just come back from doing fieldwork in Kenya with a large bulge on the back of my knee. As far as I could tell it was either a cyst (no big deal) or it was a swollen lymph node reacting to an infected cut on my knee. Infections that begin in Africa can be nasty so I wanted to see a doctor to make sure I didn’t need antibiotics to kill Lake Victoria parasites that may have entered my bloody soccer-wounded knee. (Thank you Google for making me crazy, but not crazy enough to call a homeopath.)

Anyway, I needed to see a doctor to ease my mind. I felt fine. But I’d feel stupid if I didn’t see a doctor and it turned out that I had microbes or worms or some other awesome parasite. I’d never had a bulge on the back of my knee and coming home from Western Kenya with a bulge where there are lymph nodes was too much of a coincidence to ignore.

(Yes, secretly I wanted to have a parasite. It’s complicated.)

I found a General Practitioner with offices in the same building as my gynecologist. I booked an appointment, explaining my knee, and it seemed normal like all appointments I’ve made with doctors before.

But when I arrived at the office I could tell something was different from everything before. There were quotes on the walls about the soul and the spirit (not Jesus, God, or the Holy Spirit) and there was a dream catcher hanging in one of the corners, but what tipped me off that I wasn’t exactly in Medical Kansas anymore was the tiny TV pointed at the waiting room chairs.

The volume was so high that I couldn’t concentrate on filling out the paperwork. I asked the receptionist to please turn it off, but she only turned it down. The speaker on the TV was weaving a story about a patient of his. This man had experienced decades of mysterious illnesses and after seeing a plethora of doctors who could not diagnose, relieve, or cure anything, he was cured when he came to see the speaker, an osteopathic doctor. Now the man can walk again. After this story, the speaker/doctor stood over a different patient, felt around his liver, and diagnosed his immune disease.

At this point I was sure I did not want to be there and was pretty angry that I got lured into this scene from my medical insurance’s website. So I stood up and asked the receptionist about the last question on the forms, hoping to get out of this appointment on technical grounds rather than potentially embarrassing merit ones. “I thought this was covered by my insurance. Why does it say that it may not be? I can’t be here if it’s not covered.”

She didn’t know the answer so she pulled the doctor out of her appointment with a double amputee who I’d seen go back there earlier. The doctor, a friendly hippie, assured me that she wouldn’t do anything that wouldn’t be covered by my insurance.

At this point, since she’d seen me, I couldn’t run away. So I signed the waiver and waited. Just before I worked up the courage to slip out the door, they called my name and I was led to the cluttered examination room.

The doc made small talk. She seemed nervous like a rookie would be, not like the 55+ woman that she was. She glared at me head to toe and then complimented my eyes. She weighed me, got my height, then asked me what was wrong. I told her about my knee. Usually when I say, “...and since I just got back from Africa…” the doc’s eyebrows arch and s/he gets excited or worried or both. But she didn’t flinch a bit and Africa was never spoken of again. So I’m thinking, okay, I’m a hypochondriac – it must be a common cyst. I guess I was still thinking she’d do real medicine since they give osteopathic medicine degrees from prestigious and accredited universities all over this country. I thought she must be okay.

I laid down face-down on the bed so she could feel the back of my knee where it was swollen. She asked me if, “you’ve ever had your teeth braced”. Although I thought the wording was odd I replied, “yes” and noted this as professional jargon. She continued, “Because that means that you have some inherent asymmetries,” and apparently the ones in the teeth indicate asymmetries are throughout the body and these cause problems. She then linked this to my knee problem. No mention of a cyst even as she felt the bulge.

I understand how asymmetries can cause biomechanical issues, etc… but the guy on the video in the waiting room linked asymmetries to cancer. I was very uncomfortable by now, but all of this was too weird and wild to miss. This was the single most bizarre medical experience I’d ever had so I went gleefully along for the ride and pretended to be a cultural anthropologist (but a bad one who didn’t practice disclosure) or an undercover journalist. But I didn't have to pretend that I was anything because I was an actual Science Spy.

She asked if I’d ever had any operations or surgeries in my life. Obviously this has nothing to do with diagnosing and treating a cyst. I told her about my tonsillectomy. I added, “And knee surgery,” but on the other knee, as I pointed out, and not on the knee in question. This, she loved. See? My asymmetries were playing out all over the place. Her story was coming together beautifully. Her case for giving me her special treatment was building, evidence was mounting.

“Well,” she asked, “do you mind if I check something? Can you lay down face-up please?” She twisted my feet so that my legs twisted all the way from my hips. The right one with the cyst didn't twist as far as the left one. Hmmm. Something’s up. This little gumshoe medical mystery was getting exciting. So I fed the bear some more.

When she asked me if I’ve had any back troubles, I told her all about the slipped discs in my neck. She ate it right up. This is exactly what she wanted to hear. The picture was getting clearer and clearer. It was all making sense now.

“Do you mind?” As I was still lying down, she held my head in her hands and twisted my head to the right and to the left. She noticed that she couldn’t twist it as far to the right side. There was that darn asymmetry again.

“Okay," she said, "can I do something else?” This is when she put her right hand over my right hemisphere and her left over my left and then she pulsed her hands in concert with the energy pulses emanating from my brain.

The problem was... my brain's hemispheres weren't pulsing in sync.

So naturally the next thing you’d want to do in this situation is rub my hip with a vibrator. And that’s what she did. Both hips. For about 10 minutes on each side while we chit-chatted about all kinds of fun stuff. She was a really nice woman. It felt marvelous.

Then she re-checked my legs. Both twisted just fine now. She re-checked my brain waves. Both sides pulsed in sync now. She re-measured my height. I was taller now!

No mention of what could cause the bulge in my knee or how to deal with it. Just, “It was great to meet you and let’s do a follow-up soon to see how that knee is doing. Maybe do another treatment in a couple days. Let’s put you down on the calendar.”

We made a follow-up appointment. I knew it was all a lie and that I was going to cancel it, but after she’d used a vibrator on me, I felt like I had to make a second date.

I called back that afternoon and told the receptionist, that aw shucks I actually can’t make that appointment. The doctor called me back each day for the next three days and in her messages she asked how my knee was doing and she acted hurt and concerned that I’d canceled our follow-up. Her last message was pretty prickly.

As Google informed me, swollen lymph nodes take 12 days to shrink back to their normal size and by day 12 the bulge on the back of my right knee- whether it was a cyst or a swollen lymph node - was gone and the infected cut on my knee was healed as well. This was just 4 days after my vibration treatment.

Osteopathy worked!