Could Emotions Trigger Allergies?

This is quite fascinating! Hmmm I’m going to try and see about my allergies which I developed when I moved out of Buffalo. Interesting, very interesting!

https://www.bphope.com/blog/could-emotions-trigger-allergies/

The intense emotions associated with bipolar may cause allergies to flare up.  Pinpointing a traumatic experience and talking it out may help.

Photo: PeopleImages/Getty Images

By Lynn Rae

For this blog post, I am going to take you back in time to the 1970s.  I am going to show you that allergies are really our emotions in disguise, in my experience.

I was a teenager.  I rebelled against authority, but only in small ways.  My mother still ruled and I was afraid of her wrath if I did anything wrong.  Smoking cigarettes was the cool thing to do at that time.  It began innocently enough for me.  I was only 12 and a friend came to our cottage with me.  I tried smoking, but couldn’t inhale.  But I was hooked.  I kept trying to smoke and I was going to learn to inhale.  By the time I was 16 I was smoking regularly, perhaps 2-8 cigarettes a day.

Then I met the man, who was to become my husband. He smoked a pack a day. By the time I was 19, I was smoking that much too.  I really don’t know why I enjoyed it so much.  It is only in the last few years I have come to understand that all my emotions went up in smoke.  I smoked when I was happy, sad, mad or glad.  I smoked to celebrate the beginning and end of the day.  I smoked on my coffee break and lunch hour from work.  If I was angry with my husband or some other family member, the first thing I did was reach for a cigarette.  With every inhale and exhale, my problems seemed to disappear.

By the time my son was 3, he was fascinated with cigarettes and the ashtray.  One thing I didn’t want was for him to become a smoker.  A hypocrite was something I was not!  I quit smoking in the spring of 1988 when I was pregnant with my daughter.  For three days, I lay on the couch in the fetal position having withdrawal.  It was tough, but I was determined to quit for my kids’ sake.  Exactly six weeks after I quit smoking, I was visiting a farm and my nose started running.  It wouldn’t stop.  I went through a box of tissues in 24 hours.  I went to see my doctor.  He said I had allergies.  I shook my head in disbelief.  How could this be?  I quit smoking to get healthy and this is what I get?  I took allergy pills and/or a needle for a few years.  Every time I walked by the perfume counter in a store I would start to sneeze.

Over a 15-year period my allergies eventually subsided.  I didn’t need to take medication for them anymore.  During this time, I was diagnosed with depression, then bipolar disorder.

This is when the real work on myself began.  I read over 200 self-help/motivational books, attending workshops and support groups, left my marriage and began to rebuild my life.

Since 2005 I have had very few problems with my allergies acting up.  Also by 2005, I had resolved every issue I had with people in my life to the best of my ability.  I knew that getting out of toxic relationships and/or jobs was the key to my well-being.  As a side effect, my allergies cleared up as well.

Fast forward to the summer of 2008.  I met a man and fell in love with him very quickly.  However, he was never available.  I didn’t want to believe he was married, but the signs were all there.  But there was something about this man that captivated me.  I wanted him more than I have ever wanted a man.  But all I got was the leftovers.

A few months later he was going away on business.  I told him when he got back he had to decide; it was her or me.  Finally, I had to accept that we would never be together.  When I tried to accept this fact, my sinuses started acting up.  I hadn’t been bothered by allergies for four years.  My nose just ran and ran and ran over a 24-hour period.  I couldn’t sleep, I was so stuffed up.  I tried working, but had to come home.  I could hardly breathe.  I took some over-the-counter medication, but it didn’t help.  I told my girlfriend how I was feeling.  She let me talk and talk and talk.  When I finally was all talked out, my allergies eased up.

Now fast forward to 2015.  I was slightly hypo-manic and decided to contact him.  I hadn’t thought about him in years, but for some reason I needed him again.  Once again, we started up a relationship.  However, by this time he had left his wife a year earlier.  Of course, I was daydreaming about how we would one day live together.  When, once again, I realized he was just using me, and my allergies acted up.   It was only when I could let him go that my sinuses cleared up again.  I have seen over and over again that when I am really upset about something, my nose gets stuffed up.

You see, when we smoke, we are smoking all our emotions away.  When I quit smoking in 1988 there was nowhere for my emotions to go because I didn’t know how to talk to people about what I was feeling.  We didn’t talk about problems in our family; problems got swept under the rug hopefully to be forgotten about and go away on their own.  It was only when I learned to talk about anything and everything that was bothering me that my allergies disappeared.  They only rear up once in a while, but don’t last for more than a day or two because I can usually pinpoint what the issue is and talk in out with a trusted friend.

If you are bothered by allergies, go back to when they started.  What triggered them?  Do you agree or disagree with my opinion about why we get allergies?

Irritated, Angry and Aggressive Bipolar Disorder

https://www.bphope.com/blog/irritated-angry-and-aggressive-bipolar-disorder/

My friend and fellow blogger, Julie Fast (info below) wrote this article. And it is truer than true. The intensity behind our anger, the strength, is unbelievable! And yes medications that control mood can be very helpful but sometimes, anger will slip by. Vigilance, behavior modification and medication are all needed to put this genie back into its bottle.

Unfortunately, aggressive irritation is, quite often, a symptom of bipolar disorder.

Aggressive irritation is a unfortunate symptom of bipolar disorder. It often comes with a down swing or a mixed episode where you’re manic and depressed at the same time.

We all experience irritation- that’s a normal part of life. Getting cut off on the free way- rude people- crowds and long lines at the supermarket can make us irritated. We may mutter under our breath and give a lot of dirty looks when we get in these situations.

Bipolar aggressive irritation is different- it has a lot of strength behind it. Instead of just getting irritated when we get cut off on the free way- we yell and scream, honk the horn and if it’s particularly bad- actually chase down the person with our car. Oh yes, this happens!

If someone is rude to a person in an aggressive irritated mood swing- they had better watch out- we may say, “What the @$@#$#@ are you looking at! You have a problem with me!” And we will move in on them and practically growl.

Bipolar aggressive irritation is different– it has a lot of strength behind it

Some other signs of this aggressive irritation: throwing things- such as wanting to throw my $%#%% computer across the room when the internet won’t work!  Or feeling my head and neck jerk because I’m so angry at something.

This is NOT good stuff, but it’s common.

If you love someone with bipolar, especially a man in his 20s, this may be all too familiar.

Here is some good news. Medications can work wonders with irritation.  Then behavior modification has to become a part of life.

When I get irritated, angry and aggressive, I have learned to calm myself down- and at least stop myself before I take my aggression too far!

Julie

Julie A. Fast is the author of Loving Someone with Bipolar Disorder, Take Charge of Bipolar Disorder, Get it Done When You’re Depressed and The Health Cards Treatment System for Bipolar Disorder. She is a columnist and blogger for BP Magazine and won the Mental Health America journalism award for the best mental health column in the US. Julie was also the recipient of the Eli Lily Reintegration award for her work in bipolar disorder advocacy. Julie is a bipolar disorder expert for the Dr.Oz and Oprah created site ShareCare. Julie is CEU certified and regularly trains health care professionals including psychiatric residents, social workers, therapists and general practitioners on bipolar disorder management skills. She was the original consultant for Claire Danes for the show Homeland and is on the mental health expert registry for People Magazine. She works as a coach for parents and partners of people with bipolar disorder. Julie is currently writing a book for children called Hortensia and the Magical Brain: Poems for Kids with Bipolar, Anxiety, Psychosis and Depression. You can find more about her work at www.www.JulieFast.com and www.BipolarHappens.com

Faulty Support Cells Disrupt Communication in Brains of People with Schizophrenia

This research shows that schizophrenia may NOT be the result of abnormalities in neurons, but actually abnormalities in cells that support neurons. These cells are Glial cells or Glia. Glia includes two major types: astrocytes and oligodendrocytes.  Astrocytes are the brain’s principal support cells, while oligodendrocytes are responsible for producing myelin, the fatty tissue that, like the insulation on electrical wires, wraps the axons that connect different nerve cells.   The source of both these cells is another cell type called the glial progenitor cell (GPC).

When the production of glia is abnormal, there is less connectivity and nerve impulses are not optimal.

When glial cells from schizophrenic people are turned into pluripotent stem cells and then Glial progenitor cells and injected into brains of neonatal mice, these mice show all the symptoms of schizophrenia, they were more fearful, anxious, anti-social, and had a variety of cognitive deficits. While mice who were implanted with glial cells that were from normal people did not show these symptoms.

So this a very interesting finding, that the support cells may well be involved in the development of schizophrenia!

This could lead to new, and hopefully better, ways of treating people with schizophrenia.

Please read below for more details.

SCHIZO

https://www.urmc.rochester.edu/news/story/5101/faulty-support-cells-disrupt-communication-in-brains-of-people-with-schizophrenia.aspx

New research has identified the culprit behind the wiring problems in the brains of people with schizophrenia.  When researchers transplanted human brain cells generated from individuals diagnosed with childhood-onset schizophrenia into mice, the animal’s nerve cell networks did not mature properly and the mice exhibited the same anti-social and anxious behaviors seen in people with the disease.

“The findings of this study argue that glial cell dysfunction may be the basis of childhood-onset schizophrenia,” said University of Rochester Medical Center (URMC) neurologist Steve Goldman, M.D., Ph.D., co-director of the Center for Translational Neuromedicine and lead author of the study which appears today in the journal Cell.  “The inability of these cells to do their job, which is to help nerve cells build and maintain healthy and effective communication networks, appears to be a primary contributor to the disease.”

Glia are an important family of support cells found in the brain and play a critical role in the development and maintenance of the brain’s complex interconnected network of neurons.   Glia includes two major types: astrocytes and oligodendrocytes.  Astrocytes are the brain’s principal support cells, while oligodendrocytes are responsible for producing myelin, the fatty tissue that, like the insulation on electrical wires, wraps the axons that connect different nerve cells.   The source of both these cells is another cell type called the glial progenitor cell (GPC).

Astrocytes perform several functions in the brain.  During development, astrocytes colonize areas of the brain and establish domains in which these cells help direct and organize the network of connections between nerve cells.  Individual astrocytes also send out hundreds of long fibers that interact with synapses – the junction where one neuron’s axon meets another’s dendrite.  The astrocytes help facilitate the communication between neurons at the synapses by regulating the flow of glutamate and potassium, which enable neurons to “fire” when they are communicating with each other.

In the new study, the researchers obtained skin cells from individuals with childhood-onset schizophrenia and reprogrammed the cells to create induced pluripotent stem cells (iPSC) which, like embryonic stem cells, are capable of giving rise to any cell type found in the body.  Employing a process of first developed by the Goldman lab, the team manipulated the iPSCs to create human GPCs.

The human GPCs were then transplanted into the brains of neonatal mice.  These cells out-competed the animal’s own native glia, resulting in mice with brains comprised of animal neurons and human GPCs, oligodendrocytes, and astrocytes.

The researchers observed that human glial cells derived from schizophrenic patients were highly dysfunctional.  The development of oligodendrocytes was delayed and the cells did not create enough myelin-producing cells, meaning signal transmission between the neurons was impaired.

The development of astrocytes was similarly tardy so that the cells were not present when needed and were thus ineffective in guiding the formation of connections between neurons.  The astrocytes also did not mature properly, resulting in misshapen cells that could not fully support the signaling functions of the neurons around them.

“The astrocytes didn’t fully mature and their fibers did not fill out their normal domains, meaning that while they provided control to some synapses, others had no coverage,” said Martha Windrem, Ph.D., with URMC’s Center for Translational Neuromedicine and first author on the study.  “As a result, the neural networks in the animals became desynchronized and uncoordinated.”

The researchers also subjected the mice to a series of behavioral tests.  They observed that the mice with human glial cells from individuals diagnosed with schizophrenia were more fearful, anxious, anti-social, and had a variety of cognitive deficits compared to mice transplanted with human glial cells obtained from healthy people.

The study’s authors point out that the new research provides scientists with a foundation to explore new treatments for the disease.  Because schizophrenia is a unique to humans, until now scientists have been limited in their ability to study the disease.  The new animal model developed the by the researchers can be used to accelerate the process of testing drugs and other therapies in schizophrenia.  The study also identifies a number of glial gene expression flaws that appear to create chemical imbalances that disrupt communication between neurons.  These abnormalities could represent targets for new therapies.

Resilience

What is resilience? It’s the ability to bounce back after an adverse event. Like a rubber band snaps back to its real shape after being stretched to the limit.

We have resilience. Some of us have more, some of us have less. At times we have lots of it, at other times, we have a little bit.

Sometimes we may be seriously resilience challenged and sometimes we may be blessed with lots of it.

Of course, no matter what happens in our lives, what matters is how we react to it. Easy to say. Sometimes we may feel we don’t have any control over our reaction to an event, that the event is so awful that all we can do is break down. But… but we always have control over how we react. Maybe not the initial reaction, but certainly the ensuing reaction, after we think about what has happened and how it affects us. At that point we can decide how to react and push ourselves towards resilience, towards getting over it, towards being strong and tall.

Intranasal formulation of ketamine helps clear treatment-resistant depressive symptoms

There are estimated to be 6 million people are in the US alone who have treatment resistant depression.

The authors of this study have shown that esketamine, a component of the anesthetic ketamine, in the form of a nasal spray, can bring people out of treatment resistant depression! They hope to bring this into clinics soon. This would be a godsend for people with treatment resistant depression!

Ketamine works by binding NMDA receptors, not neurotransmitter receptors like conventional antidepressants do.

http://www.psypost.org/2018/01/intranasal-formulation-ketamine-helps-clear-treatment-resistant-depressive-symptoms-50520#

A ketamine-based nasal spray produces rapid improvement of depressive symptoms, according to new research published in the scientific journal JAMA Psychiatry.

The double-blind, randomized, placebo-controlled study of 67 adults with a diagnosis of major depressive disorder examined the effects of esketamine, a component of the general anesthetic ketamine.

“Depression is the number one cause of disability worldwide,” remarked study author Ella J. Daly, a researcher at Janssen Pharmaceutical Companies.

“The development of a novel, safe and effective treatment for patients suffering from treatment-resistant depression (TRD) is a recognized significant unmet medical need,” Daly told PsyPost.

“Currently, about one third of patients with major depressive disorder do not respond to treatment with conventional antidepressant medications, leading to continued suffering for patients and their families and significant direct and indirect costs to society. In the US alone, it is estimated that there are approximately 6 million people with treatment resistant depression.”

Previous research had found that ketamine produced an antidepressant effect in patients with treatment-resistant major depressive disorder. Ketamine interacts with NMDA receptors in the brain, meaning it works differently than conventional antidepressant medications that influence serotonin.

The new study, which was a Phase 2 clinical trial, tested disposable nasal spray devices that delivered a dose of esketamine.

“The intranasal formulation that we are studying is less invasive compared to an intravenous formulation, and may facilitate ease of access in outpatient settings,” Daly explained.

In the study, the participants received 28-mg, 56-mg, and 84-mg doses of esketamine twice weekly. All three doses produced an antidepressant effect. The participants were given esketamine in addition to their currently existing antidepressant treatment.

The drug was generally well-tolerated. But four participants experienced adverse effects that led them to drop out of the study. The most common adverse effects were dizziness, headache, and dissociative symptoms.

“Intranasal esketamine is being developed as a treatment for adults with treatment-resistant depression (TRD). Ongoing phase 3 studies are under way to demonstrate safety and efficacy and to better understand the optimal duration of treatment,” Daly said.

“Of note, in a separate program, Janssen is also evaluating intranasal esketamine as a treatment for patients with major depressive disorder and imminent suicidality.”

The study was funded by Janssen Research & Development, which hopes esketamine will become a medically-approved treatment.

“The results of this study reinforce the potential of esketamine as a treatment for patients with treatment-resistant depression and support further clinical research, providing hope for people in need,” Daly said.

“If approved by the FDA, esketamine would be one of the first new approaches to treat refractory major depressive disorder available to patients in the last 50 years.”

The study, “Efficacy and Safety of Intranasal Esketamine Adjunctive to Oral Antidepressant Therapy in Treatment-Resistant Depression A Randomized Clinical Trial“, was co-authored by Jaskaran B. Singh, Maggie Fedgchin, Kimberly Cooper, Pilar Lim, Richard C. Shelton, Michael E. Thase, Andrew Winokur, Luc Van Nueten, Husseini Manji, and Wayne C. Drevets.

Feeling Down? Scientists Say Cooking and Baking Could Help You Feel Better

Ok people take out the flour, butter and eggs, put on your gloves and start baking, cooking, all of these will make you feel better, more in control and happier even the next day! And there really is a journal called The Journal of Positive Psychology! Happy baking, cooking and creating! ‘Tis the season 🎄

https://www.smithsonianmag.com/smart-news/feeling-down-scientists-say-cooking-and-baking-may-help-you-feel-better-180961223/?utm_source=facebook.com&utm_medium=socialmedia

Cooking or baking has become a common cure for stress or feeling down, but there might actually be some science to why small creative tasks might make people feel better. According to a new study, a little creativity each day can go a long way towards happiness and satisfaction in the bustle of daily life.

The study, published in the Journal of Positive Psychology, suggests that people who frequently take a turn at small, creative projects report feeling more relaxed and happier in their everyday lives. The researchers followed 658 people for about two weeks, and found that doing small, everyday things like cooking and baking made the group feel more enthusiastic about their pursuits the next day, Daisy Meager reports for Munchies.

“There is growing recognition in psychology research that creativity is associated with emotional functioning,” Tamlin Conner, a psychologist with the University of Otago in New Zealand and lead author on the study tells Tom Ough for The Telegraph. “However, most of this work focuses on how emotions benefit or hamper creativity, not whether creativity benefits or hampers emotional well-being.”

By following detailed diaries kept by the study subjects, Connor found that in addition to feeling happier, people who worked on little creative projects every day also felt they were “flourishing”—a psychological term that describes the feeling of personal growth. That could mean that the good feeling that comes with pulling a freshly-baked loaf of bread out of the oven could carry over into the next day, making that baker more likely to keep on with their little acts of creative cooking, Ough writes.

This isn’t the first time researchers have drawn a line connecting making food with positive feelings. In recent years, psychologists have started spending more time exploring cooking and baking as a therapeutic tool to help people dealing with things like depression and anxiety, Meager reports.

“When I’m in the kitchen, measuring the amount of sugar, flour or butter I need for a recipe or cracking the exact number of eggs—I am in control,” baker John Whaite, who won “The Great British Bake Off” in 2012, told Farhana Dawood for the BBC. “That’s really important as a key element of my condition is a feeling of no control.”

For people like Whaite, who was diagnosed with manic depression in 2005, baking can help their mood by providing small tasks to focus on in a manner similar to meditation. In order to put together a good meal, cooks have to be constantly in the moment, adding ingredients, adjusting the heat of the stove and tasting their food to make sure everything will come out alright—all of which can be helpful techniques in treating some forms of mental illness, wrote Huma Qureshi for The Guardian in 2013.

“A lot of us turn to baking when we’re feeling low,” Melanie Denyer, the founder of the Depressed Cake Shop, a bakery designed to draw awareness to mental health conditions, tells Dawood. “Some of us even started baking because they were ill and needed something simple as a focus.

Baking may not be a be-all-end-all cure for mental illness, but anyone in need of lifted spirits should consider pulling out the flour and warming up the oven.

How Our Brains Inhibit Our Unwanted Thoughts

GABA, an inhibitory neurotransmitter is involved in intrusive thoughts, rumination and even hallucinations. If the levels of GABA are low in the hippocampus, then it will be difficult to control our thoughts. GABA, GABA, my kingdom for GABA!

https://www.technologynetworks.com/neuroscience/news/brain-mechanism-that-inhibits-unwanted-memories-uncovered-293915

Scientists have identified a key chemical within the ‘memory’ region of the brain that allows us to suppress unwanted thoughts, helping explain why people who suffer from disorders such as anxiety, post-traumatic stress disorder (PTSD), depression, and schizophrenia often experience persistent intrusive thoughts when these circuits go awry.

We are sometimes confronted with reminders of unwanted thoughts — thoughts about unpleasant memories, images or worries. When this happens, the thought may be retrieved, making us think about it again even though we prefer not to. While being reminded in this way may not be a problem when our thoughts are positive, if the topic was unpleasant or traumatic, our thoughts may be very negative, worrying or ruminating about what happened, taking us back to the event.

“Our ability to control our thoughts is fundamental to our wellbeing,” explains Professor Michael Anderson from the Medical Research Council Cognition and Brain Sciences Unit, which recently transferred to the University of Cambridge. “When this capacity breaks down, it causes some of the most debilitating symptoms of psychiatric diseases: intrusive memories, images, hallucinations, ruminations, and pathological and persistent worries. These are all key symptoms of mental illnesses such as PTSD, schizophrenia, depression, and anxiety.”

Professor Anderson likens our ability to intervene and stop ourselves retrieving particular memories and thoughts to stopping a physical action. “We wouldn’t be able to survive without controlling our actions,” he says. “We have lots of quick reflexes that are often useful, but we sometimes need to control these actions and stop them from happening. There must be a similar mechanism for helping us stop unwanted thoughts from occurring.”

A region at the front of the brain known as the prefrontal cortex is known to play a key role in controlling our actions and has more recently been shown to play a similarly important role in stopping our thoughts. The prefrontal cortex acts as a master regulator, controlling other brain regions – the motor cortex for actions and the hippocampus for memories.

In research published today in the journal Nature Communications, a team of scientists led by Dr Taylor Schmitz and Professor Anderson used a task known as the ‘Think/No-Think’ procedure to identify a significant new brain process that enables the prefrontal cortex to successfully inhibit our thoughts.

In the task, participants learn to associate a series of words with a paired, but otherwise unconnected, word, for example ordeal/roach and moss/north. In the next stage, participants are asked to recall the associated word if the cue is green or to suppress it if the cue is red; in other words, when shown ‘ordeal’ in red, they are asked to stare at the word but to stop themselves thinking about the associated thought ‘roach’.

Using a combination of functional magnetic resonance imaging (fMRI) and magnetic resonance spectroscopy, the researchers were able to observe what was happening within key regions of the brain as the participants tried to inhibit their thoughts. Spectroscopy enabled the researchers to measure brain chemistry, and not just brain activity, as is usually done in imaging studies.

Professor Anderson, Dr Schmitz and colleagues showed that the ability to inhibit unwanted thoughts relies on a neurotransmitter – a chemical within the brain that allows messages to pass between nerve cells – known as GABA. GABA is the main ‘inhibitory’ neurotransmitter in the brain, and its release by one nerve cell can suppress activity in other cells to which it is connected. Anderson and colleagues discovered that GABA concentrations within the hippocampus – a key area of the brain involved in memory – predict people’s ability to block the retrieval process and prevent thoughts and memories from returning.

“What’s exciting about this is that now we’re getting very specific,” he explains. “Before, we could only say ‘this part of the brain acts on that part’, but now we can say which neurotransmitters are likely important – and as a result, infer the role of inhibitory neurons – in enabling us to stop unwanted thoughts.”

“Where previous research has focused on the prefrontal cortex – the command centre – we’ve shown that this is an incomplete picture. Inhibiting unwanted thoughts is as much about the cells within the hippocampus – the ‘boots on the ground’ that receive commands from the prefrontal cortex. If an army’s foot-soldiers are poorly equipped, then its commanders’ orders cannot be implemented well.”

The researchers found that even within his sample of healthy young adults, people with less hippocampal GABA (less effective ‘foot-soldiers’) were less able to suppress hippocampal activity by the prefrontal cortex—and as a result much worse at inhibiting unwanted thoughts.

The discovery may answer one of the long-standing questions about schizophrenia. Research has shown that people affected by schizophrenia have ‘hyperactive’ hippocampi, which correlates with intrusive symptoms such as hallucinations. Post-mortem studies have revealed that the inhibitory neurons (which use GABA) in the hippocampi of these individuals are compromised, possibly making it harder for the prefrontal cortex to regulate activity in this structure. This suggests that the hippocampus is failing to inhibit errant thoughts and memories, which may be manifest as hallucinations.

According to Dr Schmitz: “The environmental and genetic influences that give rise to hyperactivity in the hippocampus might underlie a range of disorders with intrusive thoughts as a common symptom.”

In fact, studies have shown that elevated activity in the hippocampus is seen in a broad range of conditions such as PTSD, anxiety and chronic depression, all of which include a pathological inability to control thoughts – such as excessive worrying or rumination.

While the study does not examine any immediate treatments, Professor Anderson believes it could offer a new approach to tackling intrusive thoughts in these disorders. “Most of the focus has been on improving functioning of the prefrontal cortex,” he says, “but our study suggests that if you could improve GABA activity within the hippocampus, this may help people to stop unwanted and intrusive thoughts.”

This article has been republished from materials provided by Cambridge University. Note: material may have been edited for length and content. For further information, please contact the cited source.

Schmitz, TW et al. Hippocampal GABA enables inhibitory control over unwanted thoughts. Nature Communications; 3 Nov 2017; DOI: 10.1038/s41467-017-00956-z