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“Papers are like buses. None for ages and then they all come at once”. (Frazier-Wood, 2011).

It’s true, and I would like to see a Maths / Physics study on that comparable to the actual buses one :).

But yes, while I am very happy with my postdoc (which, I hope, is drawing to an end within the next 9 months) it has been marked by some publication.. ahem… difficulties. Really a factor of changing fields I think, and taking time to build up a support team in my area of research (NMR data) and really grapple with what are the burning, and unanswered, questions at the moment. But, things are looking up, so hot off the press, the latest findings are:

Frazier-Wood et al, Lipids in Health and Disease

My main research program seeks to understand how lipoprotein (think particles, in the blood, that carry the VLDL, LDL and HDL cholesterol [as well as other substances] that we are all so used to) particles can be used to mark disease and assess disease risk. It is my feeling from the literature that measuring cholesterol (even non-HDL) is not as sensitive a measure as measuring lipoprotein density (this reflects the cholesterol content of the particle) and the numbers of lipoproteins in the different SUBfractions: HDL is a fraction of lipoprotein, but my work breaks this down further and looks at HDL1-3, where the designation to class 1,2 or 3 is based on size. This ‘makes sense’ because we know that some subfractions associate with disease state more than others.

Interestingly, changes in lipoprotein size do not just occur with cardiovascular disease; they also change within insulin resistance (which is a risk factor for cardiovascular disease). Indeed, the earliest and most sensitive manifestation of insulin resistance may be seen in these lipoprotein abnormalities. Previous research had shown that insulin resistance was marked by smaller LDL and HDL particles. Some research had indicated that it might be marked my larger VLDL particles.

This paper argues that larger VLDL particles may only mark insulin resistance, when they occur in conjunction, with smaller LDL and HDL particles. In fact, this rarely-occurring pattern marks a very severe form of insulin resistance. What is the point of this? Well, one day in may help us identify those in early insulin resistant states, and treat them. In the meantime, it may help us understand the risk factors (genes [see post on my previous paper showing this does actually work]/ diet / demographic factors) that contribute to insulin resistance risk, if they associate with these lipoprotein changes. As much of my future research is based on this data, I am SUPER HAPPY to see this paper finally come out.

Frazier-Wood, Bralten et al, American Journal of Medical Geentics: Part B

In my former life, I developed new biomarkers of ADHD to be used in subsequent gene-hunting studies seeking to identify the genes associating with ADHD. My theory (and that of others) was that ADHD had too many different behaviours, was too different in different people, and too infleunced my cultura

to use the diagnosis of the disorder in gene-hunting studies. Therefore, what we need to do is identify behaviours, which we may not “see” in the same everyday way, which occur in ADHD and use these. My main candidate was Reaction Time Variability – basically, when you ask someone to complete a fairly simple computer-based task, how variable the time it takes them to respond it. The attention deficits combined with the impuslivity in ADHD mean that the child will sometimes respond very quickly, and other times take a lot longer. So goes my theory anyway, and so went my theory that Reaction Time Variability would be a good candidate for gene-hunting studies.

So… I conducted a gene hunting study, using Reaction Time Variability an lo – I found a new gene region potentially associated with ADHD. Whoop! Now, I say ‘I’ but really this was a huge collaborative effort spanning many continents, and I am especially indebted to Janita Bratlen, Alejandro Arias-Vasquez and Nanda Rommelse for their wonderful statistical help and guidance and out-and-out work. It was a great chance for me to learn how to co-ordinate data and results and interpretation across four countries and see it completed so successfully. On a more personal note, it was wonderful to see the prelim theory development during my PhD actually work in analysis. Very happy. *does a little dance*

Cheung, Wood et al, Journal of Child Psychology and Psychiatry and Allied Disciplines

This is a neat little paper. It looks at the overlap between reading disability (from two scales) and ADHD, and why they occur together so frequently, and whether IQ has anything to do with it. In our analysis the answer was: nay. In my PhD I was one of the first to publish data which went against the (then) current conception of lowered IQ being part of the core deficit of ADHD. I showed in many samples and occasions, that it really is separate,  and so we must look elsewhere to understand the cognitive profile accompanying ADHD. This paper supported that, showing for the first time, that reading deficits do not occur in ADHD because of the genetic etiology of a lowered IQ. That is quite separate to the genetic etiology of ADHD and reading difficulties.

Obviously I am happy to see my work expanded upon and replicated, and to get another paper. But, on a personal note this was one of the first student dissertations supervised by me (I taught the twin modeling aspect) and I so pleased it came out as so successful. Celeste (Cheung) was a wonderful student: always met deadlines, never had to be ‘chivvied’, never gave up and always asked for help in a good way (here is the question, here is what I have done to address it, here are my outputs from such attempts, and here is the ‘missing piece’ in my knowledge). Celeste is based in London, and she responded to distance learning unbelievably well – she learned model fitting way better like that than I ever did in person while on very expensive courses 🙂

So… what’s next? Do I get to put my feet up and drink mulled wine by a log fire and await the approaching Christmas with joy in my published-heart? Sadly not. I had a book chapter due today (first draft), which I got off a day early (whoop!) but it sucked the life time out of me for a few days, and I need to play catch up.

I am still searching for a job, and my applications are also pretty time consuming. Although, now the Sept round is over, there are a worrying lack of positions.

And, in a meeting with my mentor yesterday, she casually (as big-shot PIs can) mentioned that she wanted me to submit grants for January and February deadlines. Ouch. With my gun-ho “grants must be completed as a postdoc, as if you were a faculty. It is good training!” attitude, I may have created a monster. I think I am actually going to go for it: I’ll spend the next 2 / 3 days tidying up some current analysis (I hope this involves submitting 2 more papers and sending another out to co-authors for internal review), and meeting previous commitments in my role as ‘general statistical geneticist’ helping statgen methods be accurately and sensitively applied to real world data. Then, I’ll make a plan. A timeline, and an idea, and I’ll draft a ‘support group’ (a lucky group of senior people who have no idea what they are info) and give it a go. I am generally pro writing grants in a postdoc, although at the moment, with faculty interviews and apps, I am a little concerned about finding time to get Science done. But… I also generally do what my mentors explicitly ask, so looks like many-a-late night is to come. Poor Wesley. I know he feels like panel 2 of this (yes, I have posted it previously. I can repeat. It’s my blog.):