julie.a.ashworth

A new study of more than 300 women suggests that exposure to certain phthalates -- substances commonly used in food packaging, personal-care and other everyday products -- could be associated with miscarriage, mostly between 5 and 13 weeks of pregnancy.

The risk of a financial crisis is substantially higher than previously estimated, according to new research that accounts for multiple levels of interconnectedness in the financial system.

A new study led by a sleep researcher supports what parents have been saying for centuries: to avoid getting sick, be sure to get enough sleep.

Scientists have predicted how biological circuits generate rhythms and control their robustness, utilizing mathematical modeling based on differential equations and stochastic parameter sampling.

Biologists and engineers have developed a new non-invasive image processing technique to visualize embryo formation. Researchers were able to see, for the first time, the movement of all of the cells in living mammalian embryos as they develop under the microscope. This breakthrough has important implications for IVF treatments and pre-implantation genetic diagnosis. In the future, this approach could help with embryo selection to improve IVF success rates.

Diets rich in fish oil versus diets rich in lard (e.g., bacon) produce very different bacteria in the guts of mice, reports a new study. The researchers transferred these microbes into other mice to see how they affected health. The results suggest that gut bacteria share some of the responsibility for the beneficial effects of fish oil and the harmful effects of lard.

Dramatic research has shown that during pregnancy, cells of the fetus often migrate through the placenta, taking up residence in many areas of the mother's body, where their influence may benefit or undermine maternal health.

Probiotics show no benefit for preventing or eliminating gastrointestinal colonization with drug-resistant organisms in patients in the intensive care unit compared to standard care, according to new research.

The carbohydrate-insulin hypothesis of obesity states that carbohydrates (particularly refined carbohydrates and sugar) are the primary cause of obesity due to their ability to increase circulating insulin, and that the solution to obesity is to restrict carbohydrate intake.  Numerous studies have tested this hypothesis, more or less directly, in animals and humans.  Despite the fact that many of these studies undermine the hypothesis, it remains extremely popular, both in the popular media and to a lesser extent among researchers.  A new human trial by Kevin Hall's research team at the US National Institutes of Health offers very strong evidence that the carbohydrate-insulin hypothesis of obesity is incorrect.  At the same time, it offers surprising and provocative results that challenge prevailing ideas about diet and weight loss.
Read more »

Conventional wisdom demands skepticism. Whether it’s the official stance on high-fat diets (“they’ll give you heart disease, don’t work, or do work but not for long!”), exercise (“you must jog at a moderate pace for an hour a day, four days a week!”), organic food (“it’s nutritionally identical to conventionally-grown food!”), or sun exposure (“you must always wear sunblock!”), I always question conventional wisdom. And when it’s lacking (as is often the case), I rightly skewer it.

I’m going to do something a little different today. I’m going to look critically at conventional wisdom, but of a different sort: the kind espoused by the alternative health crowd.

Now, I’m usually sympathetic to them. We align in many ways, perhaps more often than not. We both prefer organic food, wild seafood, and sustainably-raised livestock. We both understand the benefits of smart sun exposure, spending time in nature, and getting ample amounts of sleep. But when it comes to conventional alternative wisdom regarding genetic modification of food — that it makes food unsafe and unhealthy — I have to put on my skeptic’s hat and take a closer look. This is what I do. And don’t worry; in doing so, I’ll also explore the flip side — that GMOs are absolutely, perfectly safe.

I’ve talked GMO before, but the subject hasn’t gone away. If anything, it’s even more prominent a topic of discussion, with articulate salvos fired from both sides of the argument in recent weeks. Today, I’m going to wade in. I can’t promise a final word on all GMOs for all time. I can promise a balanced, level-headed approach to a very testy topic.

So let’s examine some of the arguments commonly provided by people worried about the health effects of GMO foods.

“They’re not safe.”

Well, which ones aren’t safe? GMO is a broad category.

“Bt corn isn’t safe.”

Bt corn is a GMO with a gene insertion coding for production of a bacterial toxin that targets insects. However, this isn’t a novel toxin. The bacteria that produces it — Bacillus thuringiensis — wasn’t created in a lab, and it’s even used by organic farmers as an effective insecticide.

Okay, but Bt toxin applied in powder or spray form can theoretically be removed with washing or processing. If GMO Bt corn has it baked into the DNA, we can’t avoid it. Isn’t that bad for us? After all, Bt toxin is designed to rupture the guts of the insects it targets, and we’re always emphasizing the importance of a healthy, intact gut lining.

Bt toxin is only activated in alkaline digestive systems. Human and other mammalian guts are acidic and thus resistant, while insect guts are alkaline and thus susceptible. And not even every insect seems to be susceptible; bee foraging behavior appears to be unaffected by Bt corn pollen (PDF) and bees with no exposure to Bt corn still show up with Bt toxins in their guts because the bacteria producing the toxin is so common in nature. Bacteria also appear to be unaffected by Bt toxin, indicating a lack of danger to our gut bacteria.

The specificity of action and lack of effect on mammals or non-target microorganisms (soil/gut bacteria) that made Bt toxin so attractive to organic farmers as an external insecticide makes it non-problematic for me as a genetic modification.

“But a Canadian study found Bt toxins in the blood of pregnant and non-pregnant women.”

Here’s the paper. There are serious doubts about the validity of the levels and the tests used to measure them. Plus, since organic farming uses Bt toxin and given the lack of food intake data, we don’t know the actual source of the Bt in the serum. It could have been organic produce. It could have indeed been Bt corn. Even then, there’s still no evidence that Bt toxin is harmful to mammals with acidic guts, so I’m not sure it’s all that relevant.

However, that study did make an important finding: there were also elevated levels of two herbicides associated with GMO foods (glyphosate/Roundup and glufosinate) and their metabolites in the serum. Suspiciously, the article I linked right above skewering the Bt toxin data are silent on the glyphosate and glufosinate (another herbicide) data. They mention it but don’t elaborate. Another similar article from a pro-GMO site also fails to address the herbicide data, claiming the “post is long enough.”

“They increase the use of pesticides.”

The pro-GMO side says GMOs allow reduced use of pesticides, while the anti-GMO side says GMOs allow increased use. Who’s right?

It depends on how you define “pesticides.” If you’re talking insecticides, GMOs generally reduce the use. Bt corn is one example of a GMO crop engineered to express intrinsic insecticidal toxins, thus reducing the amount of external insecticides applied. If you’re talking herbicides, GMOs increase the use.

Overall, GMOs have led to a net increase in pesticide usage (herbicides and insecticides combined), primarily thanks to Roundup-Ready crops. Whether it’s Roundup-Ready beets, corn, soybeans, canola, or even cotton, many GMOs are engineered to thrive despite heavy and frequent application of the herbicide Roundup.

In non-resistant conventional crops, Roundup is applied very carefully:

• At planting before the crop has emerged.
• After emergence, avoiding direct contact with the crop.
• Right before harvest, when the plants are hardy and mature enough to resist it.
• After harvest, to clear the fields.

When a crop is Roundup-Ready, the herbicide can be applied continuously and indiscriminately without harming the crop. The result is often persistent accumulation of the herbicide in treated foods, as with GMO soybeans.

“Roundup isn’t safe.”

Proponents of GM technology will offhandedly mention the benignity of glyphosate, the active ingredient in Roundup. Even Charles Benbrook, a GMO critic who authored the study showing that GMOs increase pesticide usage and a letter showing the benefits to organic farming, considers it one of the safest herbicides available.

But there’s a small problem with extolling the safety of glyphosate: Roundup isn’t just glyphosate. The herbicide formula contains surfactants and other “inert” ingredients that make glyphosate better at killing weeds and, maybe, causing collateral damage. In one piece of in vitro research, scientists showed that Roundup could be up to 125 times more toxic than glyphosate to human mitochondria. Detractors will cry that the author of that paper, Seralini, is a known anti-GMO activist with serious methodological problems in his other papers (poor controls, small sample sizes, tumor-prone mouse strains). That’s probably fair. He’s not the only one, though. Earlier papers have found similar discrepancies between the effects of glyphosate and Roundup:

• Glyphosate damages placental cells; Roundup enhances the damage by increasing bioaccumulation and bioavailability of glyphosate.
• Roundup disrupts in vitro rat mitochondrial function, while glyphosate has no effect.
• Glyphosate has no toxic effect on frogs, while Roundup is highly toxic to the moist little guys.
• Protozoans, a type of microorganism, tolerate glyphosate but not Roundup.

Those studies aren’t evidence that Roundup is harming us, but they do show that studies using isolated glyphosate don’t give the whole picture.

“Roundup damages gut bacteria.”

Roundup kills weeds by disrupting the shikimate pathway (PDF), a pathway involved in the biosynthesis of several crucial amino acids. Human cells are relatively unaffected by the herbicide because our cells don’t use the shikimate pathway. There’s nothing to disrupt. All good?

Bacteria also employ the shikimate pathway, and we’ve got an awful lot of them living inside our bodies and handling some very important tasks, including immune function, digestion, production of neurotransmitters, mood regulation, and many more. This means our gut bacteria may be susceptible to Roundup residue on the foods we eat (and the air we breathe, the water we drink, and so on). This isn’t a big issue for people eating primally because the biggest offenders are Roundup-Ready soybeans and corn (and all the related food products) – two foods you likely aren’t eating regularly, if at all. That said, your exposure may be elevated if the food you eat eats a lot of Roundup-laden soy and corn (PDF), like CAFO livestock, dairy, and battery-farmed poultry, all of which may show traces of glyphosate.

Interestingly, a recent paper showed that those very same bacterial species that are reduced in celiac disease – lactobacillus, enterococcus, and bifidobacterium – are the ones most susceptible to glyphosate, while the pathogenic bacteria like salmonella and clostridium botulinium (responsible for botulism) are highly resistant to glyphosate (PDF). Furthermore, glyphosate also inhibits the anti-pathogenic activity of enterococcus bacteria. One of the reasons why “beneficial bacteria” are so beneficial is that they tend to keep the pathogens at bay, and glyphosate directly interferes with it.

“Genetic engineering is different from traditional breeding.”

Yes and no.

In nature, mutations to genes begin at the local level. Genes mutate, creating new alleles, and if those mutations confer survival benefits, the organism possessing them may pass the mutated alleles on to its offspring and, eventually, the species. Traditional cross-breeding co-opts this process, speeds it up, and isolates it, but at the core it’s essentially the same thing. If cross-breeding or natural evolution creates a trait dangerous to humans, we’ll often adapt to it, develop ways to mitigate its harm, or discontinue its use. Either way, the damage is contained to the area of adoption — which for thousands of years of agriculture was relatively small in scope.

Genetic modification in the lab allows instant adoption of new mutations. Once the seeds have been approved for commercial use, they are dispersed to any farm that can afford them. Within a few years, people all over the world are consuming foods that include the new mutation. If that mutation poses a threat to human health or the environment, it becomes a global threat because the scale and speed of laboratory genetic modification is many times larger than that of a naturally-occurring mutation. Traditional forms of genetic engineering (selective breeding of plants to amplify desired traits) begin locally and develop over many generations, giving the environment and its inhabitants plenty of time to adapt to the new mutation or stamp it out. Natural evolution proceeds over an even-longer timescale on the order of hundreds and thousands of years. In the case of GMOs, once the seeds have been approved for commercial use, mutations are global and instantaneous.

I haven’t seen any strong evidence that existing GMO foods introduce traits that are directly dangerous to humans, but the potential exists. If a GMO is going to be problematic over the long term, and these problems aren’t acute enough to show up in safety studies, there might not be enough time for us to adapt.

“Inserting one gene can affect multiple traits, not just the target trait.”

The common misconception about genes is that a single gene affects a single trait. In reality, multiple genes can determine single traits, and single genes can affect multiple traits. Pleiotropy is when a single gene affects more than one seemingly unrelated trait.

Of course, this also holds true for traditional selective breeding. Breeding tomatoes to be sweeter might alter other traits dependent on the “sweetness gene.” And theoretically, genetic engineering should allow greater control over unwanted pleiotropic effects, while selective breeding is more of a shotgun approach with more chances for unwanted pleiotropic effects.

“We need long-term human studies.”

I agree. Unfortunately, we can’t have human studies the way we can with mice. We can’t (and wouldn’t want to, of course) wean babies onto 35% GM soybean diets, track them for several decades, “sacrifice” them, and dissect their internal organs for evidence of pathology.

“I went GMO-free and feel better than ever!”

Say your average relatively uninformed consumer hears about GMO dangers, decides to go on a GMO-free diet, and Googles “gmo free diet.” What does the first result tell them to do?

1. Go organic.

2. Load up on fruits and veggies.

There you have it: going on a GMO-free diet works, for the vast majority of people, because it promotes consumption of organic food, including meat, dairy, fruits and vegetables (which we know are higher in phytonutrients and lower in pesticide residues). It’s not an even exchange for GMO-free versions of common GMO-replete foods. A GMO-free diet almost always works out to be an overall healthier and vastly different pattern of eating that ends up looking a lot like the Primal Blueprint.

“So you’re saying GMOs are safe?”

Not exactly.

I worry about the world’s food supply being controlled by a single company, or an oligarchy of companies.

I worry about the Roundup-Ready gene allows farmers to spray willy nilly. I worry about it ending up in my food and, ultimately, my body. More than anything, I worry about the effect it might have on my gut bacteria.

I worry about the scale and speed at which genetic modifications can be adopted across the globe and hope current testing protocols are sufficient to catch any dangerous ones.

But I don’t see any major issues with the process of genetic engineering in and of itself.

Don’t get me wrong: I avoid GMO foods when I can. But not because I fear genetic engineering. Genetic engineering has the potential to do some really cool things, provided we get it right, like the folks who made low-PUFA, high-MUFA soybean oil.  I avoid GMOs because I don’t want to consume Roundup, which as far as I can tell likely causes most of the problems linked to GMO foods. Because I don’t eat very much corn, soy (except for natto, and the only natto I’ve found without junk in the ingredients uses organic soybeans), sugar beet (I much prefer organic beets from the farmer’s market with the greens still attached; if you’ve never had beet greens, sauté them up in olive oil with some garlic and serrano chiles for an arguably superior alternative to spinach and kale), canola oil, or cotton (tastes terrible).

Oppose specific GMO foods. Explain why you don’t want Roundup-Ready beets and soybeans in your diet — because the Roundup it allows farmers to apply in ever-increasing amounts isn’t benign. Don’t rail against all GMOs because of something you don’t like in one. Don’t be like the skeptics who deride all organic foods because a study they like found identical levels of vitamin C in conventional and organic strawberries.

Genetic engineering isn’t inherently harmful to human health. It’s weird. It’s new. And putting a bacterial gene in your carrot or whatever sounds crazy, but it’s not necessarily bad.

What do you think, everyone?

Prefer listening to reading? Get an audio recording of this blog post, and subscribe to the Primal Blueprint Podcast on iTunes for instant access to all past, present and future episodes here.

This gorgeous fish soup is quick and easy to make, rich in flavor, and filled with healthy fats. It’s also really delicious; a weeknight meal you’ll want to make over and over again But the real reason to check out this recipe is that it’s a perfect example of how (and why) you should cook with unrefined red palm oil.

Unrefined red palm oil is incredibly dense with antioxidants and vitamins. Full-spectrum Vitamin E, co-enzyme Q10, betacarotenes, vitamin A, and vitamin K…they’re all there in abundance. There’s no secret to cooking with red palm oil, just use it in the same way that you use coconut oil, butter or olive oil. Sauté anything in red palm oil (meat, seafood, veggies, eggs), use palm oil to roast vegetables, or add it to soups or stews.

In this recipe, red palm oil is added at the end to give the soup broth an incredibly rich, velvety texture. But what about the flavor, you ask? It’s true that the strong flavor of unrefined red palm oil can take some getting use to. If you find it off-putting, then look for brands like Nutiva (our favorite) that put the oil through a cold-filtration process that mellows the flavor considerably. Nutiva’s unrefined red palm oil has such a mild flavor that it’s barely even noticeable.

Whichever brand you buy make sure it’s unrefined red palm oil, which delivers the most nutrients. To insure that your purchase of palm oil is not harmful to wildlife and does not contribute to deforestation or habitat destruction, look for brands that are orangutan-safe and habitat friendly.

This coconut fish soup with red palm oil is really great when made with firm-fleshed white fish (like halibut), but can also be made with salmon, shrimp or mussels.

Servings: 4

Time in the Kitchen: 45 minutes

Ingredients:

• 1 ½ pounds boneless, skinless fish, cut into 2-inch pieces (680 g/5 cm)
• ½ teaspoon kosher salt (2.5 ml)
• Juice from 2 limes (about ¼ cup) (60 ml)
• 2 tablespoons coconut oil (30 ml)
• 6 garlic cloves, finely chopped
• 1 small onion, finely chopped
• 2 red bell peppers, thinly sliced
• 2 plum tomatoes, cored and chopped
• 1 cup fish or chicken stock (240 ml)
• 1 13.5 fl oz can full-fat coconut milk (400 ml)
• 2 tablespoons unrefined red palm oil (30 ml)
• ¼ cup finely chopped cilantro (60 ml)

Instructions:

In a large bowl, season the fish with salt and pour the lime juice on top. Set aside.

Heat coconut oil over medium heat in a deep pot or Dutch oven. Add garlic and onion. Sauté until onion is soft, 5 minutes.

Add bell pepper and tomatoes. Cook 5 minutes, then add the stock, coconut milk and palm oil. Bring to a boil, then add the fish and lime juice.

Simmer until fish is cooked through, about 6 minutes. Add salt to taste and top with cilantro.

Joining AT&T is about to get more expensive, thanks to a new fee on the carrier’s contract-free plans.

Starting August 1, new subscribers to AT&T Next will have to pay a $15 activation fee, regardless of whether they buy a phone from the carrier or bring their own. If you sign up for a new line of service with Next, you pay the fee.

For now, existing Next subscribers won’t face any new fees, The Verge reports, and AT&T has yet to add any fees when upgrading to a new phone on the Next plan. However, AT&T’s website no longer specifically says that upgrade fees don’t apply, as it has in the past.

To read this article in full or to leave a comment, please click here

Yahoo reported on Tuesday an uncharacteristic rise in revenue for the second quarter, but it came with a hefty sum spent on boosting its search traffic.

Total sales for the period ending June 30 were US$1.24 billion, up 15 percent from the previous year. In the company’s announcement, CEO Marissa Mayer called it the most substantial growth in revenue in nearly nine years.

Yahoo’s revenue from search ads and display ads both grew, at rates of 22 percent and 15 percent, respectively.

It would appear that Mayer’s efforts to turn around the struggling Internet portal have begun to pay off. Yahoo has struggled in recent years to grow its ad sales and attract users to its various online properties.

To read this article in full or to leave a comment, please click here

One of the strongest safeguards of open government is the California Public Records Act, but like any powerful instrument, it can cause great damage when abused.

I was shocked on July 14 when I was informed that Shirley Dean, a former Mayor of Berkeley, has filed a Public Records Act request for hundreds of thousands of city records that will require several weeks of work by many City employees.

Her request – which the City is legally bound to fulfill – is for all records related to appointments for meetings involving the Mayor or any Councilmember for the past five and a half years. She seeks all calendars, memos and meeting notes from every appointment, as well as all emails and correspondence with other parties, “that are relative to appointments, including those seeking, confirming, mentioning and discussing appointments in any way.”(...)

Read the rest of Op-ed: Request to Berkeley is abuse of Public Records Act (492 words)

---

By guest. | Permalink | 88 comments |
Post tags: Government transparency, Mayor Tom Bates, Public Records Act, Shirley Dean

One of the delightful aspects of running an imaging facility is the sheer variety of projects coming through the door. Late last year my boss told me he'd been discussing with a group from Emory University about doing fMRI on trained dogs at our center. I'll confess to receiving the suggestion unenthusiastically, if only because I envisioned a mass of bureaucracy followed by a head-on logistical collision between the dog group and the dozens of human users. Activity at our center oscillates between hectic and frenetic, depending on the day. But, as it turned out I needn't have worried. The bureaucracy was handled admirably by the Emory folks while the logistical issues simply failed to materialize because of the professionalism of the dog fMRI team. It's been an enjoyable experience. And there are dogs. Many boisterous, happy, playful yet exceedingly well-trained dogs. Like these:



Motivation

Greg Berns (on Twitter here) at Emory decided a few years ago to do something that few thought was possible: to scan dogs with fMRI while they are awake and behaving, using nothing more than the same tactics as we prefer to use for human MRI subjects, i.e. training. No sedatives, no anesthetics. Nothing but some good old-fashioned familiarization.

But why try to do dog fMRI at all? In Greg's case the initial question was what fMRI might tell him about his own pet dog's brain. A simple example: was his dog excited to see Greg come home from work because it was the prelude to dinner - a conditioned response - or was the dog genuinely pleased to see Greg, the person, and dinner was a nice bonus thank you very much? I'll let Greg take it from here, courtesy of a recent TEDx talk:



Greg's initial dog fMRI project also featured in a segment broadcast on CBS's 60 Minutes in October, 2014.

As mentioned in the TEDx video, the project that Greg wanted to run at my center uses service dogs-in-training. All the dogs are from Canine Companions for Independence (CCI), based in Santa Rosa, CA. Ignoring Bay Area traffic our location is sufficiently convenient to conduct scans on these dogs. We also happen to have the same scanner that Greg has at Emory.


Training

In human fMRI research the vast majority of the time and effort goes into the data processing and statistics. For dog fMRI, on the other hand, there is a truly massive front end load to train the subjects to get them into the scanner in the first place. It's a huge, intricate, time-consuming undertaking with each dog going through up to three months of MRI-specific acclimatization to the sights, sounds and feel of the scanning environment. Learning the task they're to perform is trivial by comparison. But it's far from a burden. As service dogs-in-training these animals spend many hours of every day gleefully learning to locate correctly various objects left laying around the CCI campus, or how to open a door with a rope, or how to react to a fire alarm versus a door bell, or any number of other vital activities they will eventually perform out in the real world.

I got a tour of the mock scanner at CCI-Santa Rosa with Kerinne (on the right, below) and Erin, two of the awesome CCI dog trainers. You can also see Fritz, our volunteer for the day, in his kennel behind Erin's right elbow.



As with any human MRI the first task is safety. For dogs it's extra important to protect their sensitive hearing. Unlike humans, dogs tend to shake earplugs out of their ears unless the devices are literally strapped in, so the dogs are fitted with a sports wrap to hold the plugs in place:



Over the course of several weeks the dogs are trained to place their heads in a styrofoam muzzle rest positioned inside a wooden ring mimicking an RF receiver coil. They also learn a task, signaled by the trainer, that tells them when they can expect to get a small food reward. Eventually, the dogs learn to climb a set of steps and lie down with their muzzles on the chin rest while they lie still in a mock MRI, which beeps and clicks using recordings from the real thing. Unlike the real thing, however, it is perfectly safe for me to record videos from all angles and up close. Here's Fritz during a training session:





Scan day

The dogs are trained in groups, typically 8-10 at a time, to be scanned over a single weekend. On scan day the dogs are chauffeured over to Berkeley with their trainers and assistants. Luckily, not only is Berkeley a dog-friendly campus but it also has many open spaces for the CCI handlers to exercise the dogs while they wait. As you might imagine, a day trip out with their friends can get dogs pretty excited so the CCI staff have a bonus challenge to keep their charges focused. Nobody said hard work couldn't also be fun!

The setup at the scanner matches very closely that in the mock scanner, except for the addition of mats and covers to protect the magnet and the scanner suite from bits of dog treat and dog hair. We don't get too much of the latter because all the subjects get a bath the day before. Each dog is introduced to the scanner suite for a quick familiarization and as soon as the humans are ready (most delays are for the humans!) the dog goes through its now familiar routine.

Interestingly, none of the dogs scanned so far seems to be bothered by the presence of the magnetic field. Whether they sense and ignore it or cannot sense it we don't know. In any event their reactions to the magnetic field are not appreciably different than the average human subject. The advantage for the dogs, as for humans who have been trained in a mock scanner, is that they are acclimatized to the dark, confining tube that makes lots of noise. The biggest distraction seems to be the novel environment they've just experienced - the car ride, the Berkeley campus, new humans around the imaging center - but going from play mode to work mode is a quality specifically selected for in service dogs.

After trying different coil options Greg settled upon the standard Siemens 2-channel human neck coil for the dogs. It's sufficiently large and open that the dogs can lie in the sphinx position to get their heads inside, with front paws either side, and the handler can stand behind the magnet to signal the behavioral task. The neck coil generates decent images. Here's a screenshot of an anatomical scan on the left and a mosaic of EPIs on the right:




There's plenty of contrast while the spatial resolution and SNR aren't too bad for a brain about the size of a lemon. Dogs have thick skulls as well as large muscles around the head. These dogs are either retrievers or Labradors about a year old and are all fit and healthy so subcutaneous lipid signal tends to be similar to what I'm used to seeing with human heads. Fat suppression is used for EPI just as for human fMRI. Other parameters are described in this recent PeerJ paper:

Functional scans used a single-shot echo-planar imaging (EPI) sequence to acquire volumes of 24 sequential 3 mm slices with a 10% gap (TE = 28 ms, TR = 1,400 ms, flip angle = 70°, 64 × 64 matrix, 3 mm in-plane voxel size, FOV = 192 mm). Slices were oriented dorsally to the dog’s brain (coronal to the magnet, as, in the sphinx position, the dogs’ heads were positioned 90° from the usual human orientation) with the phase-encoding direction right-to-left. Sequential slices were used to minimize between-plane offsets from participant movement, and the 10% slice gap minimized the crosstalk that can occur with sequential scan sequences.

If you're interested in the entire scan protocol, including some of the earlier approaches that have been improved upon in the current experiments, there's more information in this PLOS ONE paper from 2013.


Dealing with motion

Motion is the arch enemy of fMRI whatever the species. As already mentioned, the best approach is to have compliant subjects. Greg's muzzle/chin rest design serves twin purposes. It allows the dogs to relax in a position where the head is reasonably well restrained left-right and head-tail, and it is a mark for the dogs to return to whenever they move to get a reward. As with human fMRI, watching the inline display as the EPIs are acquired is highly informative. It's not uncommon for a dog to be able to go 60 seconds with motion effects visible only at the level of the N/2 ghosts, as for a motivated human subject. And as for returning to their marks, it has to be seen to be believed. I once spent several minutes being highly amused by the ability of one dog to get a treat, swallow it and then return to the same position such that a triangle of small blood vessels ended up in precisely the same position in the same EPI slice. I had my finger on the screen as a reference. Except for the contrast changes due to blood flow in those vessels there were no other signs of life!

The EPI is run continuously while the dog does the task and gets treats along the way. The entire run is thus contaminated by numerous intended movements - for rewards - as well as the occasional unintended movement - most often a dog licking/swallowing a few seconds after returning to its mark. An observer notes the times in the scan the dog is being treated, to assist in the elimination of motion in post processing, but as with human fMRI the effects of gross head motion tend to be unambiguous whether they're intended or not. Unlike humans, however, these dogs tend not to fidget with the rest of their bodies, not even wagging their tails when they are on task. And they don't fall asleep, either.

I'm not involved in the processing so I can't comment on how well or how poorly one can chop out motion-contaminated EPI frames and splice together the remainder for analysis. A major difference with most task-based fMRI is that Greg's team simply discard the majority of frames where motion occurs. The trick, then, is to decide the cutoff for discarding data. This is the procedure outlined in Greg's most recent PeerJ paper:

Because dogs moved between trials (and when rewarded), aggressive censoring was carried out, relying on a combination of outlier voxels in terms of signal intensity and estimated motion. Censored files were inspected visually to be certain that bad volumes (e.g., when the dog’s head was out of the scanner) were not included. The majority of censored volumes followed the consumption of food. On average, 51% of total EPI volumes were retained for each subject (ranging from 38% to 60%).

Other than aggressive censoring, the time series are also motion-corrected using a 6-parameter affine registration and the motion traces are used as regressors in the statistical analysis. Standard stuff. Whether this is better or worse than what is commonly done for human fMRI I'm not qualified to say. What I do like is the expectation that a lot of data will be discarded and this is budgeted for in the acquisition. With most human fMRI the motion issue tends to be considered post hoc and rarely do people expect to throw out a lot of data.




Future developments

What could be done to improve dog fMRI? I'd like to test our ability to measure head movement with a peripheral device such as a pressure sensor placed on the chin rest. We have the equipment and we could probably incorporate the sensor, which in our case is a circular disk less than 2 cm diameter, into the chin rest in such a way that the dog doesn't even notice it. We record movement (usually chest movement for humans) using BIOPAC equipment which also records TTL signals sent once per TR during the EPI time series, so synchronization is trivial. Perhaps we could use such a measure to define automatically those segments of an EPI time series that should be thrown out, then motion-correct the remainder. We might then start to look at the effects of respiration and consider ways to further clean the time series.

There are also opportunities to upgrade the image acquisition. For a start we are using a two-channel (human) neck coil but the majority of the brain signal comes from the upper loop. This configuration negates the option to do simultaneous multislice (a.k.a. mutiband) EPI for fMRI. The size of the elements in the coil is suboptimal from a signal-to-noise (SNR) perspective, too. The open, circular geometry of the neck coil permits Greg to scan a wide range of dog sizes with the same equipment so I consider that a fixed specification for now. A coil mounted somehow to the dog's head has been considered and rejected because of the need for cabling. Cables would likely be too restrictive and/or get broken. An inductively-coupled head-mounted coil (which doesn't require a cable) might work, but it's a lot more complicated to design and getting multiple channels would be a problem. The option I've considered most seriously is a flexible "blanket" array coil, say 16 channels, that could be attached to a custom-built rigid former that allows the blanket to be mounted firmly as either a full or semicircle, easily mimicking the geometry of the current neck coil setup. A 16-channel array coil would permit a slice acceleration factor of at least R=2, perhaps even R=3 for SMS-EPI. It's something for me to consider as I see different RF coil designs become available.

I am also interested to know if we can acquire other types of functional scan from some of the better performing dogs. Both arterial spin labeling (ASL) and resting-state fMRI scans are highly motion-sensitive, but I'm fairly sure that some of the dogs would be able to remain as still as a human for the four or five minutes both of these types of scans require. Training in the mock scanner will tell us where the limits are. It might be appropriate to acquire ASL or rs-fMRI in shorter blocks with aggressive scrubbing of spoiled volumes. Scrubbing for rs-fMRI may change the nature of the data and I'm generally not a fan, unlike for task-based fMRI which can be considered as individual task blocks for statistical testing. But it could work for ASL. We shall have to try it and see.

Many pre-diabetic, diabetic, and insulin resistant people have used the low carbohydrate diet to successfully manage their blood glucose levels.  It just plain works.  FACT (P<0.05).

However, a small subset of this population fails to achieve normal fasting glucose.  This is likely due, in part, to a type of circadian mismatch induced by aberrant meal timing and excess exposure to artificial light at night.  For an extensive list of citations supporting the former, see “Afternoon Diabetes;” stay tuned for evidence of the latter.  In brief, a combination of delaying food intake for as long as possible after waking in the morning (“skipping breakfast”) and consuming most calories at night = no bueno.  These behaviors can also promote a circadian mismatch and phase delay.  Hint: eat when the sun is up; sleep when it is down.

 

 

 

Two more pieces of evidence:

Exhibit A. Influence of night-time protein and carbohydrate intake on appetite and cardiometabolic risk in sedentary overweight and obese women (2014)

 

In this study, the participants were asked to have a late-night snack about an hour before bedtime, consisting of ~30g whey protein, casein, or carbohydrate.

 

After doing this for just a few days, they all required significantly more insulin to maintain normal fasting glucose:

 

 

Avoiding carbs at night (both protein groups) seems to do slightly better regarding energy expenditure, but this doesn’t negate the impact on insulin resistance imo:

 

 

 

Elevated insulin levels are seen in the pre-diabetic state and generally precede impaired fasting glucose… pseudo-Dawn Phenomenon?

 

 

 

Exhibit B. Impact of bedtime snack composition on prevention of nocturnal hypoglycemia in adults with type 1 diabetes undergoing intensive insulin management using lispro insulin before meals (2003)

 

Admittedly, the context of this study is very different, and not at all looking at the impact of skipping breakfast + late night eating on fasting blood glucose… but it sort-of-did, albeit indirectly.

 

The bedtime snacks:

 

 

Focus on the grey areas:

 

 

Grey area = impaired fasting glucose.  Regardless of baseline fasting blood glucose (<7 mM, 7-10 mM, or >10 mM), and meal composition, eating late at night resulted in fasting hyperglycemia… consistent in two wildly different patient populations (obese/overweight women in the first study; type 1 diabetics in this study).  Ergo, this more likely reflects a bona fide circadian phenomenon.  Best advice?  Dawn is a good time to phe-NOMNOMNOM, or break your fast.  Cut down on food intake at night and I bet you’ll be hungry for it.  “Cut down” =/= skipping dinner; just keep it light and preferably prior to sunset.

 

 

Part 2. Does coffee count as breakfast?

 

Imo, a fast is broken with calories… but this is my opinion, and whether it’s BCAAs, primal coffee (with egg yolk), bulletproof coffee (with butter or MCTs), or regular coffee (with cream) hasn’t been fleshed out experimentally.  Until that is done, I don’t see anything wrong with bacon and eggs.  Or a hearty kale & mushroom omelette (hahaha “kale,” which I think tastes pretty nasty IRL).  Or whatever, just don’t avoiding eating for as long as possible after waking only to binge at night: the available evidence does not support this strategy (see above, and here).

Ymmv?  Perhaps, but it’s not scientific (or logical): if skipping BF & having late dinners is how our ancestors actually ate, it may have been the most efficient way to accumulate fat mass, in order to survive periods of famine.  (But that’s all speculation.)

At night, have a light dinner, avoid artificial light, and sleep well.  That’s all I got.

Oh yeah one more thing: some LC advocates think LC makes circadian rhythms irrelevant, or perhaps none of this applies in the context of a low insulin, ketoadapted state.  That is wrong given that many still have elevated fasting blood glucose levels… and it’s a silly notion: circadian rhythms always apply, because we’re humans, who evolved on Earth.

 

calories proper

 

 

Seriously? There are people out there who think circadian rhythms do not apply to them? Good article, Bill. https://t.co/5B6ICYTAzJ

— Anastasia Boulais (@primalmeded) July 15, 2015

Image by Anshel Sag

For hardcore PC enthusiasts, the annual Computex trade show in Taipei is the one to watch. The home base of the companies that design and make most of the world’s components and cases, Computex is the place where every PC part maker tries to outdo the other—often by showcasing modded computers from around the world that use their components. For PC case vendors, it’s half fashion show, half smackdown.

To read this article in full or to leave a comment, please click here