CCD is a syndrome. By definition, a syndrome is a collection of signs and symptoms known to appear together but that have no known cause.  Unfortunately, we can't use Koch's postulates to clearly link a causal pathogen to a disease.

The CCD Working Group issued this definition in 2009 for a diagnosis of CCD:

1. "the apparent rapid loss of adult worker bees from affected colonies as evidenced by weak or dead colonies with excess brood populations relative to adult bee populations;
2. the noticeable lack of dead worker bees both within and surrounding the hive; and
3. the delayed invasion of hive pests (e.g., small hive beetles and wax moths) and kleptoparasitism [honey stealing] from neighboring honey bee colonies."

To diagnose a hive that is in the process of failing:

"In those CCD colonies where some adult bees remained, there were insufficient numbers of bees to cover the brood [brood = baby bees], the remaining worker bees appeared young (i.e., adult bees that are unable to fly), and the queen was present.

Notably, both dead and weak colonies in CCD apiaries were neither being robbed by bees (despite the lack of available forage in the area as evidenced by the lack of nectar in the comb of strong colonies in the area and by conversations with managing beekeepers) nor were they being attacked by secondary pests (despite the presence of ample honey and beebread in the vacated equipment)."

"Bees gone" is not sufficient for a diagnosis of Death by CCD, if you are a CSI Apiarist.  The status of the brood is important. A lot of hive health is assessed by how well the queen and her minions are producing and caring for the young.

Another major complication is that beekeeping is an endeavor with an incredibly high rate of failure.  It boggles my mind that 15% hive loss yearly is NORMAL.  I don't mean hive losses from CCD--that's the rate of hive failure before CCD arrived on the scene. It's just the cost of doing business--a lot of hives don't make it through the winter.

In the last decade, that loss rate has crept up to 30%, on average, for the US.  This increase in bee deaths has been primarily driven by two bee parasites--Varroa Mites and Tracheal Mites.  Varroa mites are pretty big, compared to a bee. It's probably like having a tiny vampiric chihuahua stuck to your body.  Here, have a look:

(Also, I just SERIOUSLY creeped myself out imagining vampire chihuahuas.)

Tracheal mites live in the breathing tubes of insects, and as you might expect, severely inhibit the ability of bees to thrive.  And I'm just getting started on things that kill bees independently of CCD.  I can think of at least 20 different fungal infections, viruses, and additional parasites.  Foulbrood. Nosema.  Chronic Paralysis Virus.  I'll spare you the full list, but a LOT of things like to kill bees.

This is part of what makes teasing out the cause of CCD so difficult. It's not that there are no smoking guns; there are hundreds of smoking guns, all of which plausibly contribute to the decline of bees.  Here is the short list of contributors to CCD, ordered roughly in order of importance, based on the most recent literature:

• increased losses due to varroa mite;
• diseases such as Israeli Acute Paralysis virus and the gut parasite Nosema;
• pesticide poisoning through exposure to pesticides for in-hive insect or mite control
• habitat loss for foraging; inadequate forage/poor nutrition;
• Exposure to pesticides in the environment (including neonicotinoids)
• poor nutrition and migratory stress brought about by the increased need to move bee colonies long distances to provide pollination services.

Note that the pesticides on this list that are of most concern, and most common in hives, are the ones that we apply to the bees on purpose.  Miticides and fungicides to control parasites and diseases of bees are the ones of most concern for sub-lethal effects on the bees we are trying to protect.

Bees encounter pesticides in their environment as they look for nectar and pollen, and those get all the press.  That story fits a narrative for humans--we fear pesticides in our environment too--and gets privileged over other factors in news coverage.

What pesticides really seem to do is make everything else worse for bees. For example, three different studies this year found that exposure to pesticides increased  Nosema infections.  It's these synergistic effects that make pesticides of concern, not their ability to kill a bee outright.

One other factor that entomologists know is that a Beepocalypse is actually not new, if you look at the history of beekeeping.

Many of these historic collapses pre-date the introduction of pesticides or other modern bee culture practices that are being blamed for bee losses today.  The extent of some of those historic losses are staggering--up to 90% colony collapse in some cases.

Hopefully, this gives you a sense of just how difficult and tangled the problem of CCD is, and how very far we are from a simple linear cause --> effect relationship for this problem.  It IS hard out there for a bee.  And it's frustrating that when researchers find a new potential contributor, it's reported as "the cause" of CCD, even when the scientists involve explicitly say it isn't a cause.

We aren't kidding. It is complicated.

Next up: a brand new literature review published this month that tries to untangle the issue of pesticides and bees.

What is environmental enrichment? Environmental enrichment is the idea that the brain responds to stimulating environments, with things like decreased anxiety-like responses, decreased cognitive decline with aging, increased coping mechanisms, and even increasing cortical thickness and the birth of new neurons in the brain.

And it turns out, it might just also make you dead sexy. At least, if you're a rat.

(This rat wants you to draw him like one of your french girls. Used with permission from MysticGaia, via DeviantArt)

Mitra and Sapolsky. "Short-Term Enrichment Makes Male Rats More Attractive, More Defensive and Alters Hypothalamic Neurons" PLoS ONE, 2012.

The authors of this study wanted to see how environmental enrichment affected some very innate behaviors: sexual selection by a female, and what they call "defensive behaviors" (which I'll get to in a minute. So they set up a group of male rats, one half with environmental enrichment (a larger cage with tubes to crawl in, toys to play with, and fruity chews, because rats are nuts for fruity chews), and one with a normal control cage. After 14 days of this, they looked at how female rats responded to the males, and then looked at defensive behavior and hormone levels.

In order to look at female choice, the authors put a female in estrous in a large arena in what must have looked like a rat version of "The Bachelorette". On each side was a smaller cage containing a rat with his soiled bedding. One was an enriched rat and one was a control. The authors wanted to see how much time the female spent on each side.

(I have to say I really dislike this data display. It's needlessly confusing)

The female rats in general spent more time deal the enriched male rat, preferring him to the control. The authors hypothesize that this was due to higher levels of testosterone (the enriched rats had higher testosterone levels in response to the female), and that the females were smelling this, and finding the male rats more attractive.

I'm not sure I agree with this interpretation of the data. I agree the female rat spent more time over there, but I wonder if having the actual male rat present (as opposed to just his smelly bedding) is the best idea. After all, rats are perfectly capable of making noises to attract females, trying postures, showing activity. The activity of the males during this time was not recorded, did the enriched males perform more "come hither" behaviors? I think the results might be more clearly in favor of the smell if just the bedding were used.

The authors were also interested in what they called "defensive behaviors", behaviors in an open area or in the elevated plus maze. Normally, rats before closed, dark environments. How much they approach the center of an open arena, or the open arms of a maze, is a measure of anxiety. These rats, in contrast to other studies on environmental enrichment, showed increased anxiety-like behavior, spending less time in the open areas and more time in the closed.

The authors also looked at responses to a predator odor (bobcat, specifically).

You can see here that the enriched rats spent less time exploring the predator odor directly, but more time in a stretch-attend posture (when a rat stretches himself out, keeping his hind paws in a safe place). The authors interpret this (along with the anxiety-like behavior) as being an increase in defensive activity, and then hypothesize that these enriched rats are more manly (with higher testosterone), and predators can smell the manly, and thus are more likely to go after them, which means they need to be more defensive.

I'm more than a little skeptical about this explanation. I think the data is fine, and I'm interested that they got this increase in anxiety like behaviors, but I don't think it's an increase in "defensive" behavior. And is there any evidence that testosterone increases make male rats more likely to get eaten? They don't refer to any specifically, and I have to wonder if any exists. In fact, the presence of a female (and subsequent increases in testosterone) usually emboldens males, making them less anxious in response to predatory signs.

So what could be going on? I'm very interested by the increase in anxiety like behavior (and corticosterone, a hormone which corresponds to cortisol in humans and results in response to stress), and I wonder why they got these results, especially since previous results have shown the opposite effect. I am also interested in the female response, are the males really sexier? I would be interested in seeing how they behave when mating and how many offspring they produce. I think the data from this study is interesting, but I think the interpretations could use a lot more thought. But in the meantime, consider environmental enrichment. It might makes you sexier than the other guy.

Mitra, R., & Sapolsky, R. (2012). Short-Term Enrichment Makes Male Rats More Attractive, More Defensive and Alters Hypothalamic Neurons PLoS ONE, 7 (5) DOI: 10.1371/journal.pone.0036092

A Case Report has just popped up on the preprint queue of the Journal of Analytical Toxicology. In it, Pearson and colleagues detail three cases of fatality involving the methylone compound. For me the interest is the way this slots neatly into the Case Reports on MDMA fatalities, especially given the drug-discrimination paper that was our first introduction to the cathinones on this blog. Although there is great diversity, MDMA cases frequently involve an individual who was "found collapsed" by friends. Emergency medical services are invoked, whereupon the individuals are frequently found with high body temperature, rhabdomyolysis, hyponatremia (dilute blood) and may have seizure-like symptoms. Cardiac arrest is not uncommon during the course of care, as is cascading organ failure. Diversity rules the day. Some individuals have been rave dancing, some have not. Some were exposed to a broad array of other psychoactives. Alcohol, nicotine and cannabis are very common but you also see methamphetamine, caffeine and a list of other stimulant/entactogen/hallucinogen class drugs. The denialists like to point to the other factors as causal, insisting that "pure MDMA" is as safe as sea salt. My position is that the great similarity of clinical courses across the diversity of "other factors" makes it even more convincing that the single shared factor, i.e., MDMA, is the causal factor. ....plus there's this little thing called the preclinical literature.

As always with Case Reports, the work by Pearson et al. will be less than satisfying. It is only through the gradual building of the Case Reports and the addition of preclinical investigations that we will really know what is going on. But every journey starts with a single step....

The second case is the most canonical, to my eye. A 19 year old woman at a rave was observed to collapse, briefly recover, claim to "not feel well" and then exhibit seizure-like symptoms. She went into asystole en route to the Emergency Department and had a body temperature of 103.9 F. She was found negative for cocaine metabolite, cannabinoids,
opiates, benzodiazepines, phencyclidine, amphetamines, barbiturates, methadone and propoxyphene on immunoassay and positive for methylone and lamotrigine. Wait, what? This anticonvulsant sodium channel blocker is a most interesting finding. Was it being used intentionally (by the user or the tablet manufacturer) to modulate the methylone effect on monoamines? Perhaps. Or was she an epileptic prescribed an anticonvulsant? That would be interesting given this prior MDMA-related Case and the Giorgi et al. 2005 preclinical study.

Case 1 is a little more unusual, if we're assuming methylone acts much like MDMA. In this case a 23 year old male was acting erratically in public and was detained by the police and transported to the ED. This one sounds a bit more like a classical amphetamine case, with reports of forced restraint, combativeness and, sigh, the strength-of-five*-men thing. Initial symptoms included rhabdomyolysis, a body temperature of 105.9F, seizure and renal failure. After about 3.5 hrs of care a series of cardiac arrest/recovery events culminated in a fatal arrest about 24 hrs after admission. The blood workup detected detected methylone, dextromethorphan, cotinine, caffeine and lidocaine and the Medical Examiner ruled it due to methylone. As we've occasionally seen from the outside of the deaths of the rich and famous, the MEs are seemingly going on an assessment of drug levels to reach their decision. One might assume that the levels of the other drugs were considered to be below the threshold for causing a death. Naturally, we are in the purest speculation territory to start dreaming up drug interaction stories. For me, the strength will eventually lie in matching up the constellation of clinical symptoms with all the cases of fatality and medical emergency that involve methylone. I'd like to know a bit more about the dextromethorphan, however, given that it is degraded by the same CYP2D6 hepatic enzyme which degrades MDMA and, presumably, methylone. Dextromethorphan is also capable of causing serotonin syndrome, thus might have the same direction of effect as methylone in this context, i.e., this may support a relatively simple additive-effects conclusion.

The final case is just plain disturbing. A 23 year old male was acting erratically in an after-hours club when management had him secured to a chair in a van outside with plastic wrap. He was left there for 3-4 hours before being discovered. Paramedics found low blood pressure, weak (but rapid) heart rate and convulsions. Upon arrival at the ED, he had body temperature of 107 F and died after about 45 minutes of attempted life support. He had 0.03 g/dL blood alcohol concentration and methylone, in addition to several therapeutics administered in the ER (but might possibly have obscured recreational use of benzodiazepines and synthetic opiates). A positive immunoassay for cannabinoids was not confirmed on followup analysis.

I think you can see that being wrapped in a chair with plastic wrap for 3-4 hours in a van might have possible had effects. I'm most concerned about the physical exertion that might have been going on, much like in Case 1 in which the guy was struggling against police. The body heat has to come from somewhere and muscular exertion (due to intentional activity) could be that somewhere. Note that in Malignant Hyperthermia, seizure-like muscular contraction can provide that same input to the system. This would be relevant to all three cases.

As I mentioned above, this is the beginning of the story. By no means can three Cases nail down a connection with high confidence. But this is all strikingly familiar and dovetails with the aforementioned drug-discrimination finding and a recent report of neuropharmacological similarity of methylone and MDMA. So I'm betting we'll see more of these Case Reports of medical emergency and death that involve methylone.

And the profiles are going to look just like the ones involving MDMA.
__
*well, at least it was five, not ten.

Julia M. Pearson, Tiffanie L. Hargraves, Laura S. Hair, Charles J. Massucci, C. Clinton Frazee III, Uttam Garg, & B. Robert Pietak (2012). Case Report: Three Fatal Intoxications Due to Methylone Journal of Analytical Toxicology

Now I haven't paid much attention to my old blog for a while, but recently went back there to look for something I had written. Turns out the How Many Papers for Tenure? post had garnered a couple more comments. I was struck in particular by one:

Anonymous said...
Impact Factor and Citations are far more important. Quality over quantity. But quantity doesn't hurt.
Saturday, December 31, 2011 3:44:00 PM EST

Yes and no.

Maybe.

Well, actually, mostly no.

Certainly quality matters. So does quantity. Your tenure decision is partly in the hands of bean counters. One could certainly get past them with fewer than expected papers if the ones you had published made a positive impact on the field. Hopefully the letters written supporting you would make that very clear.

But Impact Factor and Citations?

No. Most emphatically, no.

It's widely accepted by all but some bean counters and the glamour hounds that journal impact factor correlates rather poorly with actual long-term impact upon the field. I've certainly read many, many society-level journal papers that have had a much larger, longer-lasting impact than many Glamourmagz papers. Sure, you don't want to come up for tenure with all of your papers, or even any of them, in sub-sub-sub-basement IF level journals. On the other hand, coming up for tenure with a single Glamourmagz publication isn't so good either. You want sufficient good quality publications to show that you have established a research program. One Glamourmagz publication doesn't do that.* Even worse, there are those of us that might think you're doing your trainees a great disservice funneling all of their work into a single high profile publication from which only the first and senior authors will garner credit.**

And citations? Puh-leeeeeze. Your tenure decision should ride on what you did during tenure-track. We're talking 5-6 years here, likely with most of your publications coming in the last 3 or so years. Hardly enough time for any but the rare immediate-large-impact publication to garner more than a few citations. The impact of your work should be judged by those who have been asked to write letters of support, particularly those within your sub-field, not by how many citations you might have gathered in a couple of years.

Focus on publishing X number of good quality publications pre-tenure, where X > the average number of publications the last few people in your department had coming up. If you land a Glamourmagz publication, good for you, but don't screw yourself over by focusing solely on that. And don't worry about citations. If your work is good, they'll come along eventually.

Next thing you know someone is going to suggest h-index as a measure of tenure-track success...

__________

* And doesn't do your chances of landing a grant as much good as you might think.
** If you want to offer up the multiple equally-contributing first author Kool Aid, go elsewhere.

Seemed kind of far-fetched. A publisher who was willing to that would be... gasp... giving up some control!

In a recent announcement, the American Mathematical Society informed us that their users are able to do just that.

They're not the first or only. You can roam with EndNote Web for a year. I think there is something similar with some of the Elsevier apps (maybe just scopus?). The ArtStor app used to do this (they might still... not sure).Maybe EngNetBase (but that was really clunky when I tried it).

This is nice - takes down some barriers for the users, increases usage, and still links downloads/reads to institutional subscriptions.

So while you are feeling miffed at "yet another one focused on the family" try to keep your shit together.

Is it that you are genuinely unable to get the info you need from these or another source? Or is it that you are sitting there fuming about your *perception* that the world finds your issues unimportant or is "telling you" to reproduce? Because some of that is on you and you need to deal.

Can you really not generalize the points being made for your own situation? Elder care, spouse with disability, self with disability... sure, there are differences but there are also a lot of parallels. So take the baby-focused stuff and adjust it for your situation. Interpret!

Or is it that the world does not accept your issue of "balance" as being important?

"I can't go to that meeting, I have my first Ironman that weekend!"

or perhaps,

"My pitbull needs walkies three times a day so I'll be missing for two hours at lunchtime"

yeah, good luck with that.

UPDATE: posts from microdro and BabyAttachMode. The latter reminded me that I failed to link to this trigger for the day's discussion. In it one Clara B. Jones (@cbjones1943) opines:

It is my personal opinion that the major disadvantage for females in
research science careers concerns how to arrange UNDIVIDED, UNINTERRUPTED,
FOCUSED TIME...sometimes, for protracted &/or unpredictable periods.
10. My own "solution" was to surrender custody of my children; however, I
am not recommending this choice to anyone else and know, from personal
experience, that this decision is one that most females are averse to
thinking about.

you know, in case you think *I* make outrageous statements or anything.....

Pediatric kidney disease, 1978

Arnold sometimes seemed wise beyond his years. Of course, he was being played by 10-year-old Gary Coleman who looked far younger than his chronological age. Thanks to focal segmental glomerulosclerosis (FSGS), a particularly nasty form of childhood nephrotic syndrome, and attempts to treat it, Gary's growth was stunted. His adult height measured 4 feet 7 inches, so he could play much younger characters...up to a point. He received two kidney transplants, both of which failed due to recurrent kidney disease.

The entire child cast of the show subsequently led troubled lives. Gary Coleman died in 2010 of a brain hemorrhage.

This week the face of pediatric kidney failure changed when Sarah Hyland, the older sister on Modern Family, revealed that she has lived with chronic kidney disease her entire 20 years of life. She recently received a kidney transplant from her father during the show's summer filming hiatus. 

Pediatric kidney disease, 2012

Lucky for Sarah, she had a much different condition called dysplasia. During development, her kidneys failed to form enough normal tissue to support her throughout her life. Doctors diagnosed her slowly-progressive condition at 9 years of age. She never received the high-dose steroids that gave Gary Coleman his round face. She benefited from decades of research that dramatically improved the ways we manage the growth failure and bone disorders that can accompany all kidney diseases. She will likely have excellent function from her father's kidney for many years without the appearance-altering side effects of earlier anti-rejection drugs.

We have made a lot of progress, but we need to make more. FSGS has some new treatments, but many patients still fail to respond and develop permanent kidney failure. FSGS still recurs in the transplant, killing the new kidney as it did the native ones. Dysplasia does not develop in the transplant, but other conditions may shorten the life of the replacement kidney. The side effects of anti-rejection drugs may be less visible, but their risks of infection, diabetes, and cancer still raise problems. We still have a lot of research to do.

But in my lifetime, look at the progress we have made!

My first reaction to this video was "Cool!", but my Supercoolwife was horrified. How about you, if this were your baby would you let this go on or pick him up immediately?