As we all know, plexiglass and masks are the new norm. Sometimes these shields make it difficult to understand what someone else is saying. Have you been to the supermarket and the cashier asks you a question? Their speech is often muffled and because of the mask there’s no lip reading to help you out.  You kind of get it but not quite. I had the same feeling reading a grant the other day. I read the words, but I didn’t quite “get it”. I understood the words I was reading, but the excitement of the idea was hidden behind big words, technical terms, and writing that was vague at times.  It was vague because of undefined concepts and unnecessarily complicated language. These issues, which are common in grant writing, put a barrier between the reviewer and your work. Because I was reading the grant to give feedback, I focused on what was putting the great ideas in this proposal just a little out of reach. 

Before I get into how to break down the barriers, I want to take another stab at conveying their impact. I heard on a podcast once that selling (yes, we are all salesmen) can be defined as getting someone to want to participate in your story. It turns out that this idea has a name – insight selling. Insight selling has two categories, opportunity insight and interaction insight. In opportunity insight, the customer/reviewer doesn’t realize that they have a problem. You define their problem and give them the opportunity to fix it. In grant writing this comes in the form of the ever popular “knowledge gap”. The second category of insight selling is interaction insight. According to a blog post on business.com, interaction insight is “building connections with customers by encouraging creative thinking, inspiring "lightbulb" moments and challenging assumptions.” Although barriers can impact both of these categories, the biggest impact is on interaction. You want the reviewer to have an “aha” moment as they understand and get invested in your work. The barriers, which I will talk about below, block interaction and can lead to what I call the “blah,blah” effect. You’re reading but not taking in the words – like when adults talk on the cartoon Charlie Brown. Although I am dating myself Charlie Brown is timeless, no? If you’re lost, see the link at the end of this post. 

Hopefully I’ve conveyed the importance of de-covidizing your research – unless, of course, your research is on covid. Now on to the barriers themselves. I believe there are three main barriers – big words, technical terms, and acronyms. The way you use words, which involves the deep, dark forest of grammar, can also lead to some fuzziness. I’m saving that for round two. Although big words are very important, I covered this in depth in a previous post. See Further Reading below. 
 
Technical terms
            You will need to use some technical terms, but you want to be sure that your reviewer understands what they mean. Some terms may not even be that technical, but if don’t remind your reviewers of their meaning your grant may suffer. For example, the grant I mentioned at the beginning applied ecologic concepts to bacteria, and - big surprise - used the word ecology. When I see the word ecology, I think electric cars, cows, and recycling. However, the true biologic definition was integral to the proposal, and warranted a revisit. Defining more common “technical” terms may cause some uncertainty, because you don’t want to seem patronizing by defining a term that readers in the field probably know, but on the other hand you don’t want your reviewer to incorrectly define your technical term. A good way of handling this is to “sneak in” a definition by adding it as a phrase offset by commas. This idea comes from the book Writing Science, by Josh Schimel, which I highly recommend. Here are some examples.
 
We will determine whether the cells are undergoing apoptosis, or programmed cell death, by three distinct assays. 
 
The IL-2 receptor, comprised of alpha, beta, and gamma subunits, is expressed on T cells.   
 
If you’re not sure if your reviewers are familiar with a term, the above method serves as a way to add in needed information without a separate definition. Defining terms is especially important when you are combining two disciplines, because most likely your reviewers will only be experts in one. In general, err on the side of defining technical terms. A few years ago, I submitted a grant to a cardiovascular study section and I proposed using a mouse model that caused the mouse to have increased cholesterol. I assumed that any reviewer in a cardiovascular study section would know this model so I didn’t define it. I was wrong. One reviewer, in the written feedback, did not know that this model caused an increase in cholesterol so he/she didn’t understand why I chose it. In the next grant, I made sure to define it.  
 
Acronyms and abbreviations
            Using acronyms and/or abbreviations can be a good way to save some space, but it’s a tool that must be used judiciously. Acronyms are commonly used in science, but like technical terms you need to make sure and define them, unless you think the acronym is so common that any reviewer in your field will know the definition. If you’re writing a manuscript, journal-specific instructions usually provide a list of common acronyms that you don’t need to define. These typically include acronyms such as FBS (fetal bovine serum), FITC (fluorescein isothiocyanate), etc. for those in biologic sciences. If you’re a physicist you probably have your own acronyms that I’ll never understand. For a grant, you’ll need to use your own judgement, but for the most part you’ll want to define acronyms. 
            One good way to irritate a reviewer is to introduce 2 or 3 new acronyms at the same time. Keep in mind that even though you define an acronym your reviewer has to remember what it means. If the reviewer forgets, there’s a good chance he/she won’t bother to go back and find the definition, which means he/she might get confused, and we know that nothing good comes of confusion in grants! When I say “new” acronyms, I mean an acronym that your reviewer may not be familiar with, or one that you made up to save space. What do I mean by “making up” an acronym? Making up an acronym would be akin to abbreviating the song “I Shot the Sheriff”, originally by Bob Marley and covered by Eric Clapton, to ISS. That phrase is in the song multiple times. While using an acronym would definitely save space, readers will struggle to remember what ISS means, not to mention ruining a perfectly good song. Here’s a science-based example. In the past, I worked with a molecule called heparan sulfate proteoglycan, and studied its impact on the immune system. For those in the proteoglycan field, heparan sulfate proteoglycan would commonly be abbreviated with the acronym HSPG. However, for an immunology-based grant, most reviewers would not be familiar with this molecule and might forget what the acronym means. Because of this concern, I wrote out the name rather than abbreviating. 
Despite the above rant, there are times when you’ll need to make up an abbreviation or acronym. This situation may occur if you have a new technique or molecule that you are mentioning frequently, especially if the item in question requires a lot of words or letters. Let’s say your grant has to do with the effect of the word “supercalifragilisticexpialidocious” on viewers of the film Mary Poppins. You would want to shorten this to supercal or something along these lines. Not only does this word take up a lot of space, but continuously reading it takes a lot of mental effort. To give you a more science-based example, a few years ago I wrote a grant involving a peptide that I made. Rather than describing the peptide as the “N terminal 15 amino acids of a cytokine receptor” every time I mentioned it, I made up a name – N15AA.
            Finally, if you’re going to use an acronym, make sure that you use it at least 3 times. In other words, don’t define an acronym and then use it only once. It takes up more space to define the acronym and then not use it, and you’re burning excess brain cells of your reader.
 
I hope these ideas help you dismantle barriers between your ideas and your reviewer. In Covid terms, these barriers range anywhere from a hazmet suit to a scarf-mask, but with some interim paylines in the single digits, clarity is key. Clarity comes both from reminders as to what might be confusing to a reviewer, like the above, and through awareness of the “curse of knowledge”. The curse, in which you know your work so well that you can’t appreciate what others don’t know, is very common. Getting feedback from someone less familiar with your work will make sure you ward off this evil curse. 
 
 
Further reading
 
Big Words, by yours truly. http://www.drlucywrenshall.com/grant-writing/big-words
 
Charlie Brown’s teacher talking. https://www.youtube.com/watch?v=ss2hULhXf04
 
What is Insight Selling? A Beginner’s Guide. https://www.business.com/articles/insight-selling-guide/
 
Writing Science: How to Write Papers that Get Cited and Proposals that Get Funded, by Josh Schimel.
​https://www.amazon.com/Writing-Science-Papers-Proposals-Funded/dp/0199760241/ref=sr_1_1?dchild=1&keywords=josh+schimel&qid=1603635817&sr=8-1
 
I Shot the Sheriff, by Bob Marley, sung by Eric Clapton https://www.youtube.com/watch?v=L0xLLPJ0bOw
 
 
 
 
 
 

​The significance section of an R01 is probably the most misunderstood part of the entire NIH grant. Perhaps this should come as no surprise, as this section has been a bit of a moving target over the past several years. Another source of confusion may be that Webster’s definition of significance and the NIH’s definition are “significantly” different. A brief history lesson may shed some light on why the significance section is a bit murky and will put today’s directives in context.
 


A brief history of significance
            Way back in the dark ages, when getting your NIH review in the mail as a “pink sheet”, the R01 proposal was 25 pages long. Significance was included with background, and given the overall length of the grant, background often expanded into a verbal upchuck of information about the topic at hand. In 2009, the powers that be decided to give the reviewers a break and the 25 page limit was reduced to 12. The background and significance section slimmed down and was intended to highlight key findings rather than review the world’s literature. In 2016, spurred on by the need for public accountability, NIH grants underwent a major overhaul and the significance section had a new set of instructions. Significance was to include the word premise, which was defined by the NIH as “the quality and strength of the prior research used as the basis for the proposed research question or project; this is distinct from the hypothesis or justification.” The significance section was also to describe the strengths and weaknesses of the prior research. Since these initial instructions, the word premise has been dropped and quality and strength of prior research is addressed as, wait for it…., rigor. 
Webster defines significance as “the quality of being important”. Investigators must like this definition, as most significance sections that I have read include something about the importance of the work. However, the NIH forgot to check Webster’s, and if you only include statements about the importance of the work your significance section will miss the mark. The NIH assumes success of your specific aims and wants to know “how will your work, successfully carried out, impact the field?”. I put the word successfully in italics, because if your work is founded on weak preliminary data and/or a poor approach, successful completion of aims will not have a major impact on the field.  
 
Significance today
      Knowing the evolution of the significance section might explain the potential differences that you’ll see either as a reviewer or in reading examples of successful grants. Now let’s head back to the future. What are reviewers looking for in today’s version? The current significance section looks for impact based on the rigor of prior research.  What is rigor of prior research you ask?  Right from the horse’s orifice of choice, rigor of prior research is defined as “the quality and strength of the research being cited by the applicant as crucial to support the application; this is distinct from the hypothesis or justification.” It’s premise without the word premise. 
            As part of the rigor of prior research, the applicant is supposed to address the “strengths and weaknesses of the prior research used to support the application and describe how the proposed research will address weaknesses or gaps identified by the applicant. This may include the applicant’s own preliminary data, data published by the applicant, or data published by others.” Here is your opportunity to discuss the strengths of your preliminary data (for an R01) or published data (R21, R03) that are the foundation of your hypothesis. The weaknesses you will, of course, be addressing in the grant.  
 
Structuring your significance section
            Although the exact order isn’t critical, the elements described above must be included in your significance section. I suggest starting with a brief paragraph restating the critical need your proposal addresses and how successful completion of your proposal will change the field. Remember, this is the NIH definition of significance. If you have a surprising statistic that supports the need here’s the spot.  In the next paragraph restate the hypothesis, followed by the strengths of your key supporting data. I don’t think it’s over the top to include a sub-header entitled “Rigor of prior research”.  It’s hard for a reviewer to claim this wasn’t addressed when you have it written as a separate section.  From there you discuss the weaknesses, which prepares the reviewer for the approach section where they will be addressed. 
 
Here’s an example of a significance section, which is taken from a proposal using e-yarn as a way to detect lost socks. This example highlights my approach, but as the saying goes, there are many ways to skin a significance section.
 
Socks are the number one lost laundry item in the United States. Every household is, at some point, plagued by the problem of lost socks. Lost socks generate substantial psychological and financial burdens on many households, which escalate exponentially in families with 8 feet or more. Last year alone, replacement costs for lost socks reached 1.2 million dollars, and this cost is on the rise. Experts from the Simpson Family Foundation, a think tank focused on family issues, project that by 2040 the problem of lost socks will surpass health care as the number one drain on family budgets. New ways to find lost socks must be found now to avert this future financial catastrophe.
 
Rigor of prior research: We hypothesize that socks made with e-yarn will be detectable within an average size US home (2000 sq feet) using a barcode cell phone application. This hypothesis is built on strong data demonstrating that detectability of e-yarn is resistant to dye (Figure 1), water (Figure 2), and that 1 g of e-yarn is currently detectable up to 2000 feet (Figure 3). Based on these data, the proposal that follows will develop a unique, cost effective way to find lost socks. Successful completion of this proposal will represent a significant step towards eliminating the financial and psychological burden of lost socks. A side benefit of this approach is that, if desired, family members with similar sized feet can identify their own socks. Finally, this technology can be applied to other problematic clothing items such as cufflinks and earrings. 
This proposal will address the following weaknesses in preliminary and published data. Our preliminary data shows that 1 g of e-yarn is detectable by RFID up to 2000 feet. However, we have not yet tested smaller amounts of e-yarn. Since it is not cost effective to make an entire sock of e-yarn, we will determine the smallest amount of e-yarn that can be woven into a sock and remain detectable. This question will be addressed in Aim I. 
Many studies have taken a compensatory approach to the problem of lost socks rather than finding the sock itself, which is the goal of this proposal. Some studies, for example, suggest that purchasing a 6 pack of socks can address the lost sock problem.2-5 However, these studies have only used white athletic socks and do not take into account more expensive dress socks. Another approach, reported by Hanes, et al, was to wear mismatched socks.6 However, their study was limited to 15-25 year olds, who have been shown to enjoy wearing mismatched socks.7-9 A similar approach, wearing only one sock, was supported by findings of Scholl, et al.10 However, this study involved a more sedentary population. When tested in a younger, more active population, Adidas et al found that the one sock approach was not feasible due to foot sores and odor, particularly when studied in student athletes traveling together on buses.11,12
 
As outlined above, this example starts with a restatement of the problem, adding a little more detail than what was presented on the specific aims page. From there, I restate the hypothesis, so that it is fresh in the mind of the reviewer as he/she goes on read the key data supporting your hypothesis. These key data are the “strength” of the strength and weaknesses of supporting data. Make sure that you demonstrate the strength of your data with figure legends that support rigor and reproducibility (positive and negative controls, statistics, numbers of replicates and experiments/animals, etc). After listing the key supporting data, I describe what will happen upon successful completion of the proposal. Because this section focuses on the proposal, rather than the problem, the successful completion part flows nicely from here. I then finish by discussing the weaknesses/gaps that will be addressed.
 
Where’s the background?
            Since the NIH got rid of the “background and significance” section it’s dealer’s choice as to where to the background. Do you even need a background section and if so, how much? Yes, you need some background information. I think of background as a “need to know” section. Include what the reviewer needs to know so that he/she understands your work and its context. Some investigators still put this information in the significance section, and others put it at the beginning of the approach. I do not recommend putting your background with the significance, because you risk reviewers missing the information the NIH asks for (and you are scored on) by getting caught up in background details. 
 
If nothing else, remember that the significance is the impact of your proposal, if completed successfully, on the field. Reviewers are instructed to score grants with this idea in mind. Now time to do some laundry.

​Last time we chatted, or I like to think of it as chatting, I talked about feeling powerless. For me, feeling powerless is something I have struggled with throughout my life, and these “unprecedented times” have no doubt fostered that feeling in many people. If you think some of your unhappiness is due to feelings of powerlessness, what can you do?  It’s easy – stop thinking about it! You can thank me later.
 
Ok, so of course it’s not that easy. If it was, we’d all be like our dogs and cats, enjoying the sunshine, getting excited about a squirrel, and then going back to sleep. Actually, there’s no magic bullet to annoying, unpleasant or harmful thoughts - followed soon by their sidekick feelings - but awareness is half the battle. After countless books, podcasts, and courses, my Sparks notes summary to dealing with thoughts comes down to 3 major techniques: question your thoughts, mindfulness, and meditation. I know the words mindfulness and meditation have been thrown around a lot, but don’t check out yet because I have some specific suggestions as to how to use these tools. 
 
Before I get into each technique, I want to revisit this idea of powerlessness in the context of needing to control things. In Part I, I referred to Mo Gawdat’s Talks at Google about our need to control. When things are not in our control, we feel powerless. Mo doesn’t recommend abandoning all control, because some attempts at control move things forward. For example, if you live in a flood plain, rather than hoping that it doesn’t rain heavily it makes sense to exert some control through building barriers, moving etc. Rather than abandoning all control, Mo recommends thinking about the things you’re trying to control and pick a few high priority areas that you want to attempt some degree of control. I put the latter in italics because things are never totally under our control. Be aware of the cost of “control” and the cost to your happiness. This awareness might help you trim your “control list”. 
 
Let’s say you’ve narrowed down your control list to a few key items. What happens when life throws you a curveball?  (Spoiler alert: life will throw you a curveball at some point). How you respond makes all the difference. Mo uses the term “committed acceptance” and Eckhart Tolle, a well-known spiritual teacher, uses the word surrender. While both of these terms may seem to imply giving up, that is not the case. What they do mean is to stop arguing with reality, so that you can respond rather than react. Let’s say you’re on your way to an important dinner meeting with a potential employer. You’ve heard that this employer is really a stickler for being on time, so you leave a little early to make sure you’re not late. It’s raining heavily, and as you’re driving you swerve to miss a biker who can’t see well and end up on the side of the road in the mud. If you are angry and just react, you might choose to keep hitting the gas and getting even more stuck. Here is where the committed acceptance/surrender comes in. Committed acceptance helps you respond rather than react. Rather than continuing to “gun the engine” in an angry response, you accept that you’re stuck, which then allows you to take effective action such as finding some wood or cardboard, calling a tow truck, or cajoling a friend to help.
 
 If you’ve read any self-help literature, you’ve probably run across the phrase “what we resist persists”. To continue the story, let’s say you can’t get your car out and end up calling a tow truck. You call your potential employer and explain the situation. He understands but doesn’t really care – he’s left the restaurant and is no longer considering you for the position. Yikes! You “resist” this event for days, maybe even weeks – going over each step in your head. Why did I take that route? Who does he think he is? Each time you play the conversation over in your head the anger comes back. You’ve heard him tell you “I’m sorry but you’re no longer a candidate” 50 times in the past two weeks. What you resist persists. Sometimes your anger is perfectly justified. You tell several of your friends about this incident and they confirm that this guy is a total jerk. Maybe you even get so angry that you send an email specifically telling him he’s a jerk and you wouldn’t want to work for him anyway! Probably not the best move. Plus, you’ve spent a lot of energy over the past 2 weeks being angry with not much to show for it. I realize that anger can be motivating, but often anger comes from reaction rather than a place of perspective where more effective action can be taken. From a state of committed acceptance, perhaps you reach out to the potential employer and explain yourself again. Alternatively, you renew your job search, maybe even entertain additional schooling. Each of these actions are more effective than arguing with the reality of the situation and fueling your anger.
 
Committed acceptance sounds great you might say, but it’s one of those things that’s easier said than done. When something big happens, like job loss, divorce, the centennial pandemic, etc. how can you “leave it” as I tell my dog, so that you can move on to committed acceptance?
 
Well, it’s a good news/bad news kind of answer. The bad news -you can’t stop thinking. The good news  - you can be aware of and redirect your thoughts. This is a key skill for happiness. Not to go all Buddhist on folks, but thoughts are the major, source of suffering in our lives. Let me give you a brief explanation of three ways that I’ve found helpful to deal with the monkey mind.
 
Question your thoughts
Let’s go back to where we started - feeling powerless. Hopefully y’all are back in the lab full or mostly full tilt under the likely restrictions of masks, spacing, etc. During lock down, though, you may have had thoughts that the situation is totally out of your control and there’s nothing you can do. I say “thoughts” because often you have more power than you realize, but your brain is telling you that you’re powerless. Because the brain wants to be right, it then merrily goes along finding ways to back up that statement. In addition, the brain is a sifter. To make life easier, the brain filters all the stimuli that’s out there. Mostly that’s a good thing, so that once we learn to drive, for example, we don’t need to think about every little thing that goes into the complex task of driving. We just get in the car and go. However, the bad thing is that sometimes we only “see” things that back up our thoughts. If we think we are powerless, then the brain will tend to focus on things that support that statement. If that’s not convincing enough, then your brain will take you through your past and bring up experiences that support the thought. 
By questioning our thoughts, we take a step back and ask whether the thought is really true. When you tell yourself “Nothing ever goes right for me” or “I can’t get a break” ask yourself whether this is really true. Go back through your past and find examples where things did go right. The master of questioning your thoughts is Byron Katie. She developed 4 questions we can ask ourselves to help deal with undesirable thoughts. Katie also has tons of videos on YouTube where she takes folks through the 4 questions – definitely worth watching. Although questioning your thoughts is a good way to counter negative thoughts, it has another benefit which is to separate you and your thoughts. Who are you? You are the one questioning your thoughts. Separating you from your thoughts helps create perspective and objectivity so that you see your thoughts as they are rather than as “the truth”.
 
MIndfulness
Your thoughts can’t take you to shame town if you’re busy thinking about something else. Mindfulness is all about staying in the present and focusing on the here and now rather than mentally living in the past or the future. However, if you just had a big blow up with your significant other, “mindfully” washing the dishes is tough. You can try to pay attention to the smell of the soap, the slippery sensation of the soap and water, etc but you’ll probably drift back to that argument pretty quickly. Until you’re a mindfulness master, I recommend starting with something that demands your attention. For me, that’s playing the violin. Playing an instrument is demanding enough that you can’t ruminate and play at the same time. Other examples might be playing basketball, cooking, gardening – anything that takes enough of your attention that it’s hard to think about something else. 
 
Meditation
Meditation is another great way to practice distancing yourself from your thoughts, which makes committed acceptance much easier. As I’m sure you’re aware, one common way to meditate is to focus on your breathing. If you truly focus on the sensation of your breathing, you can’t think about the past or future. However, you will lose focus pretty quickly and thoughts will return. When you notice the thoughts, that is an example of awareness. You then go back to focusing on the breath, etc. The good thing about this type of meditation is that if you start doing this at home in a quiet space, you’ll may notice yourself taking a moment to focus on your breathing while standing in line at the check-out counter, while stuck in traffic, etc. Focusing on your breathing is a great way to take a “time out” when you’re having a stressful day. Like mindfulness, though, if a fresh hurt is really bothering you, focusing on your breathing is hard. For times like these, I recommend guided meditations. You can focus on the directions of someone else, which makes it a little easier to get away from your thoughts. Deepak Chopra (+/- Oprah) has a great series of meditations which are a combo of both “food for thought” and quiet time with music. These come in short (10-15 minutes) or extended (about 30 min) versions. Insight Timer is another great resource for meditations, with guided meditations, music only, and several classes. It also has a search function where you can search both type of meditation and length. The basic app is free or you can add on for $60/year.
 
Like anything that’s worthwhile, these techniques take practice. I promise the practice will be worthwhile, not only for yourself but for those around you. 
 
Questions? Comments? I’m a major introvert, so I’m always up for a conversation with myself, but sometimes it’s good to get out of the cave and connect with others.
 
Resources mentioned and more:
 
Byron Katie - https://thework.com. See also books on Amazon.
 
Insight Timer (found on the app store). One of my favorites is the Garden of Babylon by Jim Rajan.
 
Deepak Chopra meditations - https://chopracentermeditation.com. Paid on his website but many on YouTube. He also has a new book about meditation coming out Sept 22 via the big box internet store in the sky.
 
The Mind Illuminated by John Yates – great resource for those who want to delve deeper into meditation and mindfulness.
 
Song from the Cartoon Network show Steven Universe “Here Comes a Thought” https://www.youtube.com/watch?v=dHg50mdODFM. Great for kids of all ages.