Thursday, January 17, 2019

Let's talk about NGS, baby (part 2)

Find Part I here.

In late December 2018, an article was released in Genetics of Medicine reported the high healthcare costs for patients with suspected pediatric genetic diagnoses. A summary of the article can be found here, but the take-home message was one that I'm all too familiar with, which is that medical expenses can quickly get out of control when facing diseases that require long-term care. In addition to that, the longer the period of investigation leading to diagnosis, the greater the expenses, making a firm case for the urgent need for inexpensive early diagnostic tests.

Until recently, making genetic testing widely available for patients with suspected genetic diagnoses has been extremely expensive and limited due to outdated guidelines for who qualifies for such testing, fueling most insurance companies refusing to cover the costs. Never mind that some companies have artificially inflated the expense, leading to ethical debates. Within the past 5 years, there's been a dramatic shift, with companies like Invitae, Color and Veritas Genetics employing whole genome sequencing (WGS) strategies to genetic testing and precision medicine, fueling a new approach of patient-driven healthcare. The goal being a simple one: empower patients in their healthcare decisions instead of waiting for physicians (and insurance companies) to okay care based on traditional population data.

With the availability of this technology, though, has come a need for consumer understanding of what is being ordered. What is the difference between WGS, exome sequencing, traditional genetic testing and genotyping (i.e. 23andMe)? What about companies that are using NGS technologies to do tissue analysis (biopsies or blood draws)? How are (and should) samples be collected and how are these companies pairing with clinicians (or not pairing) in order to ensure that high-quality data? And what are things patients should be aware of as these tests become available?

Let's continue...
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As mentioned previously, resolving the structure of DNA lead to a shift in the science community. Knowing that DNA was the vehicle for heredity, another focus within the community that complimented the push for developing DNA sequencing technology was understanding how that information was being translated to the cells for use.

In 1958, Francis Crick authored "On Protein Synthesis," where he laid the foundation for his proposal for the Central Dogma of Molecular Biology: DNA makes RNA and RNA makes Protein. But outside of those who actively study biology, the Central Dogma is confusing given that there's usually no context for what these molecules are and what their purpose in a cell's function (let alone a person) would be.

So let's start by giving that context.

Whenever I introduce my students to DNA, I show them an image of a grand library found on most university campuses, teaming with information in the form of books and archives on every possible topic imaginable. This is what DNA is to your cell: an archive of all information possibly needed in order to generate an organism, be that a single-cell bacteria or a human being. All of the books you see lining the shelves are genes, which are heritable units of information that code for a different function/ characteristic (i.e. hair color, lobed ears, freckles, etc). More impressive to think about is that outside of a few exceptions, every-single-one of the cells in your body contains the exact same library of information, which is all tightly packaged inside that cell (we'll get to why that packaging is important later).

Despite having all this information, your cells won't use all of it. Just as most of us have areas of interest and career-focuses, such as a medical doctor won't know much of anything about corporate accounting and a licensed CPA will be inexperienced with chemical engineering, so too do your muscle cells not need the exact same information as your neurons or your skin cells or your liver cells. Yes, there will be some bits of knowledge that will be shared, but even if they do access similar volumes for the needed information, they may require different chapters.

That's where RNA comes in. The purpose of RNA is meant to make available the only information needed by a cell. Think of it as going into that grand university library, but instead of checking out the book, you are only allowed to make copies. And since going through and making copies of all the pages takes too long and leads to less available data, only the information that is needed is copied.

I'm going to back up a bit and point that up until the last decade, there were originally only 3 types of RNA (mRNA, tRNA, and rRNA) that were known and their role was solely involved with passing on instructions to make protein. Over the last decade, though, new types of RNA that don't go on to make proteins, also known as non-coding RNAs, were discovered and their presence has drastically changed our understanding for RNA's role in normal cellular functions and disease. I won't go into miRNAs, siRNAs, piRNAs, and long ncRNAs here (though you can read more here) but I will say is all RNA plays a role in determining not only what proteins are made in the cell, but also when and how long they will be around.

What are proteins? This article provides a nice overview, but the easiest way to think about them is that they are molecular machines in the cell that provide structure, carry out a function (i.e. metabolism, import nutrients, export waste, etc) or oversee regulation (balance pH, oversee product development, etc), often doing a combination of these. If you think of each of your cells as factories, with each factory being specialized depending on the cell type, you'll see similarities in how operations are performed, but you'll also see the differences that give rise to different tissue types. And though most factories need some similar things, there will be differences in the materials they need in order to generate a final product.

So what does any of this have to do with sequencing your DNA and genetic testing? Why not just sequence your entire genome to identify diseases or underlying conditions, especially now that I've told you in my previous post that the technology has advanced to the point that we can? The answer to that question gets back to understanding how your cells function. Despite the fact that all humans are ~99.6% genetically identical to one another (and I want you to sit with that as you look at everyone sitting in the room with you, realizing how closely related you are to people who look differently than you do), you also have ~ 6 billion base pairs of DNA in each of your cells (remember, you have 2 copies of your genome: one from mom and one from dad), that when put together is about 2 meters long (all the DNA in your body put together would be twice the diameter of our solar system). What that means is that despite the similarity, there's also a lot of variation. And how that variation translates is not in you and I having different genes, but there are different versions of the ~20,000 genes we have, resulting either in different versions of the proteins our cells will make (or not be allowed to make) or a disruption in timing for when those proteins are present to do their work. Two added wrinkles in all of this are that 1) outside of a few cases, most proteins work in concert with one another, resulting in genetics behind many diseases being complex and 2) we know environment can also have an effect. Illustrating this, recent work published in Nature Genetics focused on untangling the genetic and environmental ties for 560 conditions, offering more of insight into how this interplay is happening, but also highlighting we still have a long way to go for yesterday the molecular mechanisms behind many of these diseases.

Hence where the choice of WGS vs exome sequencing vs genotyping comes in. With traditional genotyping, the focus is on looking at differences in your genetic code that have known effects, usually in the form of single base pair changes called single nucleotide polymorphisms (SNPs). Because these changes are known, identifying them is quick and fairly inexpensive. The downside is that this data provides only a limited snapshot (there are ~ 4-5 million SNPs in the human genome) and doesn't explore more of the complexities surrounding many conditions. Exome sequencing focuses on sequencing only the portions of your genome that will make the proteins in your cells, thus excluding all the genetic information regulating the generation of these proteins. Those an extremely powerful approach for rare Mendelian diseases and more extensive than genotyping, exome sequencing only focuses on 1% (~ 30 million bp) of the genome, excluding all the genetic information controlling the generation of those proteins. Finally, there's whole genome sequencing (WGS), involving sequencing your entire genome and allowing researchers (and now clinicians) access to even variation in your genetic code. But with all this information comes challenges with interpretation, as the effects to all these changes are not known and even if there are known effects, it's not a guarantee that you will develop the condition, leading to questions about clinical significance.

One final caveat is that sometimes clinicians don't know what variations in your genome they are looking, so they are looking for when the RNA is present. In this case, sample collection is critical as RNA can easily be damaged and degrade, making it difficult to turn back into DNA and sequence. So in addition to the type of sequencing is taking into account sample collection to ensure good results.

A final wrinkle in all of this is whether to even consider sequence your genome. In an era where there are leaks in personal information, the fears about own's genetic code being used to discriminate are more real today than ever, meaning anyone venturing into this terrain is behooved for doing their homework ahead of time.
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As I type all of this out, it's hard not to feel a bit overwhelmed. Even for someone like me, who is used to being surrounded by information like this, I find myself nervous and second-guessing about whether I've covered this well and correctly. What's pushing me to get this information out there in this manner is the daily evidence that we are entering an era where biotech innovations can have a meaningful impact on our daily lives. And though the current focus for many in the US is on using this information to healthcare (and I encourage you to learn more about the  Precision Medicine Initiative), the truth is this is just the tip of the iceberg given I haven't even touched on gene editing.

That said, my hope is that I have made this information a bit more approachable, or at least armed you with the needed information necessary to do your own research. Because with all that is happening with this technology, it's likely it won't be long before it becomes more a part of our daily lives. And that's an exciting prospect.

Wednesday, January 16, 2019

Confronting death

It was an innocent mistake. I was excited to find a copy of the movie "Charlotte's Web," which I loved as a child and sat down with Maddy and Teddy to watch. Going through each scene, I began to remember the specifics of the story about a pig and his unusual friendship with a spider with a talent for words. I didn't think too much of it until near the end of the movie until we came to the scene where this spider announced she wouldn't be making the journey back to the farm. And suddenly, caught in a vortex I knew we had no way out of, I found myself preparing for the shock and sadness that all children face when confronted by the reality of death.

Teddy and Maddy are at an age where they are becoming aware of certain realities. Learning about Rosa Parks sparked a long conversation about fairness and equality, allowing us to begin future discussions about racism and civil rights. An evening bathtime turned into an anatomy lesson and exploring gender. And a recent interaction with some neighbor kids started the discussion about when friends don't want you to play with them and why in most moments that was okay vs in moments where it leads to bullying. Death has been a harder one, given the topic is rooted in sadness and grief.
It's also the one equalizer as it's something none of us will escape, meaning they will be facing this reality at some point, making it important to not shy away from these conversations. The problem is, how to have the conversation, given it's a topic that brings up a lot of fear. Some turn to religion to begin explaining, with images of an afterlife meant to help soothe, but though those initial explanations seem to help placate the questioners, it often doesn't prepare them for the avalanche of emotions that come when faced with death.

Why all of this is on my mind is because I'm trying to figure out how to prepare Teddy and Maddy for when Jaxson and Daisy pass. This summer, both kitties will be 16 years old, and though they are both in very good health, I'm also aware that their time with us as a family is also becoming short. Unlike when they were younger, both cats have developed their own relationship with each kid, meaning when the day comes that we say good-bye, the grieving process will also involve each of them navigating their own process. And though I cannot entirely prepare them, I also know that we need to start exposing them, talking about what death means and helping them process the emotions surrounding that reality now when it is more hypothetically.

Sitting on Grey's lap, a sobbing Maddy hugged him as she processed facing the death of a character and confronted her own fears about dying and her family dying. Instead of telling her not to worry, Grey held her as she processed these emotions, allowing a few tears to fall as they talked about how one day he would die too; why even though that would be sad that it was a part of being alive and why it was important to live our lives the best way we knew how.

Still, as important as these conversations are, and the fact that they need to continue, I feel completely unprepared to talk about all of this. Maybe because a part of me it's ready to face these realities yet, even though I'm very aware that they aren't terribly far away.

Monday, January 14, 2019

#MicroblogMondays: purposeful rituals

Not sure what #MicroblogMondays is? Read the inaugural post which explains the idea and how you can participate too.

Jess's post about rituals had me reflecting last night, remember my own crazy ones but also thinking about why we subject ourselves to such practices. All on the heels of me remembering how I shunned rituals for a period prior to embarking on creating new resolutions for this year.

One resolution Grey and I have been working hard to keep is getting outdoors a lot more than we have in the past. Despite the government shutdown, we've been working hard to locate hiking trails and local parks, finding ways to explore our surroundings without the buzz of technology in the background. 

It's not always an easy endeavor, especially following weeks where we're both feeling drained, but the benefits are always readily available as we've begun settling into something of a routine.

And I think that's the difference, compared to years past, is finding rituals that bring purpose and release. That instead of subjecting myself to practices out of a sense of obligation and guilt, that the focus is on refueling the soul.





Saturday, January 12, 2019

Let's talk about NGS, baby (part 1)

This week has turned into a busy one. With the J.P. Morgan Healthcare Conference in the Bay Area, there have been a number of announcements from local companies about funding, acquisitions and everyone reviewing what's hot (and what's decidedly not). With all this activity has come interviews and meetings for me, with recruiters and hiring managers reaching out to see if I'm interested in exploring potential fits with their organizations. The thing many have been looking at is my understanding of Next Generation Sequencing (NGS) technologies, given that this arena is decidedly in the "hot" category for product expansion.

Full disclosure: I don't consider myself an NGS expert (though I'm hoping to change this very soon). To date, I've only done one Illumina library prep and missed out on doing the sequence analysis and alignment due to moving across the country and naively believing the bioinformatics staff that the training was straight-forward (turns out it is . . . when you work with someone who is actually interested in training instead of acting like a superior snothead). All that said, one advantage I do have is I know how to present this information to an audience that isn't fluent with the jargon, walking them through what is and is not currently possible.

So the goal of these next few posts is to do just that, giving you a bit of history for context and even talking about what's coming down the pipe for diagnostics and care. Why this is important is because NGS technologies are rapidly moving into the patient care space, meaning that within your lifetime tests and screens for genetic conditions will become an option and fertility is at the top of the list. My hope is that I can at least give you a base-level of understanding; a jumping point so to speak.

For those interested, a more detailed history of DNA sequencing can be found here.

Let's begin.

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On April 25, 1953, Science Magazine published a one-page letter authored by James Watson and Francis Crick titled "Molecular Structure of Nucleic Acids: A structure for Deoxyribose Nucleic Acid." Regardless of your thoughts and feelings regarding how this work was completed, what is undisputed is that the publication of this article, followed a month later by this article published in Nature, marked an end of an era identifying and classifying the molecule responsible for hereditable information and ushered in a new era that lay the groundwork for modern molecular biology.

One immediate question was how does one "read" this molecular code within each molecule, putting together the correct combinations of A,G,T and C. What initially seems like a simple task actually proved to be quite difficult, resulting in slow and laborious work of generating some of the first DNA sequences that would often take years to complete. It would be until about 15-20 years after the structure of DNA was published that the first wave of DNA sequences technologies would online, with the development of the "chain-terminator" sequencing method, later adapted and developed to become "Sanger Sequencing," leading the charge and becoming the predominant method for DNA sequencing.



What set Sanger Sequencing apart for other sequencing technologies is it utilizes a single separation method combined and interpreting the results is pretty easy. Advances in the technique, such as moving to fluorescent dyes and a capillary system as well as the development of a fully automated DNA sequencer helped advance the technology, reducing costs to the method. Despite this, there were some serious limitations to this method, both in time, cost and labor not to mention needing a lot of DNA to complete a single reaction. Though researchers now had the ability to read DNA, creating maps for whole genomes was taking years and insane amounts of money, never mind issues with coverage and poor quality sequences. All of this limiting the impact of many research endeavors.

In the mid-1980s, as the automated DNA sequencer was coming online, a new wave of DNA sequencing technologies was being developed that would overcome the limitations of Sanger sequencing. Using enzymes that would produce light as DNA was being copied, pyrosequencing had obvious advantages over Sanger sequencing, that major one being that DNA sequencing could be analyzed in real time. Despite a real limitation of distinguishing repeating (stretches of As, Cs, Gs, or Ts), pyrosequencing offered several advantages and would lead the charge for "next-generation sequencing," resulting in a number of different platforms that would dominate the market. Arguably the most important one being the Solexia method.

I'm not going to walk you through the finer points of the Solexia sequencing, as that information is readily available on the Illumina website. By what I will say is that when Illumina came on the scene, the fields of genetics and molecular biology evolved seemingly overnight. Whereas before, sequencing was an expensive process where you only did the reactions as the last step to confirm tool generation or as part of an experiment, suddenly sequencing became part of the experiment. Genetics departments became Genomics departments and scientists were finally able to ask questions on a vastly larger scale. As Illumina developed its technology, and competing companies like PacBio (SMRT sequencing), Oxford Nanopore, ThermoFisher (Ion Torrent) as well as companies like10x Genomics and Twist Biosciences came on the scene, the cost of sequencing dropped from thousands of dollars to pennies, the amount of DNA needed to do a sequencing reaction dropped drastically, the quality of reads vastly improved and coverage hit levels previously never seen. And what use to take years was being accomplished in weeks (if not days) and instead of one single genome for reference, thousands of genomes were being made available to researchers. The sky was no longer the limit.



What all of this has meant for biomedical science is that DNA sequencing was no longer limited to the research space. Sometime in the early 2010s, I began hearing the words "precision medicine" at more and more talks, the idea being that a patient's genomic information could be incorporated into healthcare decisions, offering a more personalized care plan. Precision medicine is already being practiced for diseases like cancer, but there's been a push to expand into areas where the diseases have been more complex, such as mental health, diabetes, rare diseases, dietary issues and, of course, fertility.

But like any rapid advance in technology, the rest of the word is still catching up, leading to misunderstandings both from the general public and even healthcare workers what is and is not possible. And with that knowledge comes a realization that a patient's ability to advocate requires them not only to have a based-understanding of what can and is being done but also knowing enough about the process so they can recognize false-promises, sample collection errors (which happen way too often) and navigate seemingly scary results.

To be continued.....

Thursday, January 10, 2019

Instead of blogging....

The week has gotten away from me, filled with meetings and interviews while juggling getting the family back into the usual routine. My mind has been whirling with information, from recommendations to filling out applications to reading updates about biotechnology and recent research. All while drafting letters of support for the local teachers union and past students.

The end result has been outlines of posts in my drafts folder and generally neglecting this space, even though writing tends to be therapeutic, helping me organize the chaos floating around in my head. It's a fairly shitty realization.

I know I need to correct this, setting aside prescribed time to write. Overcoming all the chaos that makes me want to sleep most days. So I'm going to try, setting aside the needed time just as I need to continue doing so for other self-care areas of my life.


Monday, January 7, 2019

#MicroblogMondays: On the steps of City Hall

Not sure what #MicroblogMondays is? Read the inaugural post which explains the idea and how you can participate too.

The morning didn't start off well. Following a rushed drop-off for Maddy and Teddy at school, rushing to get to the BART station, learning that ALL the trains were delayed due to multiple problems, losing my seat to a man who pushed me out of the way and ending up on the wrong bus to my destination, I was feeling fairly grumpy.

Hailing an Uber to make sure I made it to my meeting on time, I found myself outside of City Hall, unknowingly becoming a witness to a celebration involving what looked like a young family with an adorable little girl who was dressed in a lovely dress and the center of attention.

I'm fairly certain what I was witnessing was a wedding reception, given adoptions are normally finalized at courthouses, but the joy that radiated around this group, all of them embracing this child had familiar feelings that this family's journey to today wasn't an easy one, hence the reason for so much celebration.

And that celebration was contagious. 

My Uber driver was insanely nice, driving like a controlled maniac to make sure I made it to my meeting on time. And the meeting was insanely good, with this new contact proving to not only be valuable but also a pretty cool human being. Both of these men noting the smile on my face, in memory of that moment on the steps of City Hall.

Sunday, January 6, 2019

Plan B

Years ago, my mother came up with the oh-so-brilliant idea that I should adopt my cousin's son. My cousin had found herself facing having custody revoked for a second time, following the state determining that she was not meeting basic standards her son needed. Fueled by panic when my ex-uncle's brother stepped up, being willing to take the child, my mom decided that Grey and I would be even better candidates to fulfill this purpose, given we were childless, struggling with infertility and preparing for IVF.

I thought about all of this last night, following reading this post on Cup of Jo that Loribeth pointed out and the recommendation to explore the comments section (side-note: it was incredibly refreshing to see so many support comments). It was one comment in particular by someone named Rita that brought all of it back. Rita starts by talking about how she and her husband turned down her BIL/SIL when asked to be their baby's in-case-of-emergency guardian and how difficult this decision was. But it was this sentence stuck with me:
"They said they thought of us “since” (??) we aren’t planning to have children, which I found most perplexing a statement because why leave a child with a couple who doesn’t want their own kids?"
Cue all the many feelings and emotions.

Assigning guardianship for minors is something I use to assume was easy. Growing up, the assumption was that you simply listed next-of-kin, be it grandparents or siblings. But that was before I began thinking about how children were raised, taking into account values and life-goals in the best of circumstances. Nevermind ending abuse cycles. The added element is seeing first-hand the generational effects when these decisions are poorly made as Grey's grandfather was orphaned at a young age, being raised by an aunt who, though she adored her own children, was far from stellar as an assigned guardian.

With all of this in mind, Grey and I have struggled for the past 5 years to assign emergency guardianship for Maddy and Teddy. Family members have been a hot topic, given that we either see them as unreliable/potentially dangerous or being completely maxed out with their own lives and families. With friends, it's been even more tricky, given that we know how life-altering this decision could be. Ideally, we want a home environment where Maddy and Teddy would be well cared for and loved without stressing out their guardians beyond repair. Hence finding a couple with one or even no children would seem initially ideal and part of Rita's comment touches on this mindset:
"They also said that they value our values, our outlook on life, our responsibility with money, level-headedness, etc. I was so anguished over this decision… my confidants tried to get me to see that this was a compliment to us."
All of this seems like a great option until one considers something equally important: those who are not parenting often suffer the misguided assumption that their lives are somehow incomplete and that introducing a child/children into their lives will magically make it whole. That and the fact that their lot in life is to be solely to be emergency guardians or some secondary role.

Even though it was years ago, I remember the acute pain I felt as my mom begged Grey and me to adopt my cousin's son so that my aunt could remain his grandmother. Nevermind all the reasons this was an insanely bad idea, the fact my mom saw me solely as a placeholder made clear what I meant to her.

Something my mom is now desperately trying to deny given how my infertility journey ended.

This morning, I told Grey it was time we finalized emergency guardians for Maddy and Teddy. Though I have my ideal couples in mind, the reality is for many this brings about some sort of assumption that they would even want this burden. And even with these initial discussions comes the understanding that if that ideally there won't simply be one set of guardians guiding these kids, just as I have that same hope now. 

Because the reality is Maddy's and Teddy's role isn't to fill some void; no more than people who are not parenting should be waiting in the wings to take on child-raising responsibilities. And those that make these assumptions need a reality check.

Thursday, January 3, 2019

Reset

The winter of my sophomore year at university, my dad gifted me a copy of the Weigh Down Diet. Always concerned with the size of my body, my mother was constantly sending me information about caloric restriction diets and tips of who to achieve a thin frame. None of which had the desired effect outside of poor body-image. So I was skeptical when I picked up this book from my dad, assuming this would be yet another fail.

I only finished the first half of the book, stopping when the author launched into incorporating the Christain faith into her philosophy, but the first half of the book immediately changed the way I viewed my relationship with food and how I viewed my body. Four months later at the end of the semester, my dad came to take me home for the summer and found me 15 lbs lighter with a new outlook on how I was feeding myself.

I've been thinking about the Weigh Down Diet over the past few years, given all the hype about Paleo, Keto, and Whole30 diet plans. The idea that certain foods are off-limits has brought back a lot of anxiety given that shame-based approaches tend to have the opposite of the attended effect. So when Cup of Jo had a post about Intuitive Eating, followed by many body positive posts, I found myself not only nodding along but also coming the realization that I was overdue for resetting my own eating habits.

So for the month of January, I'm taking a break from sugar. Currently, I'm three days into this process and suffering some serious withdrawal symptoms, which are oh so fun. But I know that without this reset, old patterns will be difficult to break making this a necessary step. In addition, I'm spending a lot of time listening to what my body is actually saying, honoring what it is asking for even though some of those desires would be considered poor ones for any of the traditional programs.

All of this is still odd, particularly given so there are many who are also embarking on their own eating-habits resolutions and this approach is very different from what they are doing. But just as I've learned to honor different aspects of other journies, so too will I be doing the same here; sharing this experience while supporting others in their own endeavors.

Tuesday, January 1, 2019

So this is the New Year

"So this is the new year
And I have no resolutions
For self assigned penance
For problems with easy solutions"

~ The New Year - Death Cab for Cutie

I'm not good with resolutions. The ideas surrounding "self-improvement" and "starting anew" usually leave me with a sense of guilt when things fall flat a few weeks out. Because of this, it's been years since I've really made a firm commitment to any lifestyle changes around this time of year all due to the realization that lasting change usually involves a lot of activation energy and shifts in mindsets, both of which requiring a lot of work.

But 2018 didn't end the way I was hoping. Yes, there's been a lot of good that happened that year, with Grey starting his current position, being rapidly tracked for leadership roles and seeing a lot of growth career-wise. And yes, Maddy and Teddy are doing amazingly well, with us not only seeing improvements following their surgeries but also thriving at school due to their teachers working with us to make sure a firm foundation is being built for their growth in the years to come. And yes, we are happy to be back on the West Coast, having easy access to hiking trails and ocean beaches while surrounded by a culture that Grey and I identify with.





But despite the good, I've been struggling. Ending my last contract after my boss changed her mind about bringing me in permanently and having to hire a lawyer to end the relationship was the wake-up call that its time to leave science education. Retooling is easier said than done, though, especially given that I don't have an industry track-record (a fairly common hurdle for anyone leaving academia that many acknowledge yet few have a solution for). On top of this, a side-product of me working with Teddy and Maddy is the realization that I likely have undiagnosed ADHD and that not addressing has actually done a lot of harm to me to date. All this on the heels of my parents recent freak-out, with me finding myself insanely angry over recognizing that not only did they miss this diagnosis with me (reminding me what a "bad child" I was and how they struggled so much with me), but also that I have to take on the role of "parent" with them, setting clear boundaries and unapologetically making it clear what is and is not acceptable.

So, this is the new year, with so much already on the horizon. Standing on the beach today with Grey, watching Teddy and Maddy play in the surf and sand, Grey and I made some resolutions about prioritizing self-care and sanity via getting lost in the woods or along the coast more and me seeking diagnosis/treatment. None of which will be done without some additional activation energy and establishing some firm boundaries.

And yet, I must confess that I'm also feeling energized to make these resolutions a reality. If for no other reason than knowing that though the self-assigned penance will require a lot of work, it is work that has clear rewards at the end.
 
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