SciBlogs

Archive 2012

Deadly ignorance John Pickering Dec 14

How many deaths does it take?  We hear that question asked time and again following a tragic event.  We also hear it with calls for changes to our public health priorities.  Well, I am now asking it with respect to Acute Kidney Injury.

  • Acute Kidney Injury (AKI) is one of the most common hospital events (4-5% of patients get it).
  • The most severe forms of AKI result in emergency dialysis.
  • Research out of the US has shown that there has been a doubling of dialysis for AKI over the past decade (1).
  • Now there are 533 cases of dialysis requiring AKI per million people each year in the US.*
  • 24% of those needing dialysis died in hospital
  • About 10 times the number who need dialysis actually get AKI.
  • Even mild AKI raises the risk of in-hospital death and long term kidney problems.
  • More people each year now have dialysis for AKI than those who start dialysis as a result of a chronic kidney disease.

Comparative New Zealand statistics

I would like to do them but have had problems getting funding.  I especially want to look to see if there are any ethnic biases in the numbers.

If we take the US numbers and apply them to our population of 4.4 Million then there would be:

  • 2350 cases of dialysis-requiring AKI of whom 564 would die.
  • Over 20,000 people each year would have AKI.  Many more than 564 would die.

My gut reaction based on the use of dialysis in the Christchurch hospital intensive care unit is that 2350 is probably too high, maybe two to four times too high.  This may reflect differences in dialysis protocols and admittance to ICU.  It is less likely to reflect a lower incidence of AKI.  My best guestimates are:

  • 4000 to 8000 cases of AKI each year with 400 to 800+ deaths.

These numbers are greater than the road toll – another acute event.

They are comparable with Breast Cancer**.

I would like them not to be guestimates.

Maybe the funding will come next year.

The good news

My research and others over the past few years has:

  • identified new biological markers of injury to the kidney
  • assessed many of these and determined that they are of clinical value
  • come up with better ways of defining the disease
  • determined that some pre-existing tools can be applied in slightly different ways to give early warning of changes in kidney function
  • come up with some promising interventions which may reduce the risk of developing AKI

Here endeth the 2012 report.

___________________________________________________________________________________________

1.  Hsu RK, McCulloch CE, Dudley RA, Lo LJ, Hsu C-Y. Temporal Changes in Incidence of Dialysis-Requiring AKI. J Am Soc Nephrol 2012; Online ahead of print.

* the data was expressed in “million-person-years” but as the data was for one year then it is OK to express it as per million people.

**The difference between AKI and many other diseases is that while AKI causes death it is almost always secondary to another event – heart attack, severe infection, cardiac surgery etc, so it is rarely recorded as THE cause of death.

Tagged: Acute Kidney Injury, AKI, Kidney, Mortality, Nephrolog

Do we talk about the right cancers? John Pickering Dec 12

We all want a cure for cancer.  This is evident in the ideas put forward for the NZ Science Challenges (http://www.thegreatnzscienceproject.co.nz/home).  Will these ideas reflect the true need in New Zealand? Are all cancers equal or are some more equal than others?  Does the public perception of what is most important reflect the true health risks?  To answer this latter question would require a well controlled survey which I don’t have.  What I can do is look at some data from the media.

First the numbers: The Table below gives the number of newly diagnosed registered and of deaths in New Zealand for various cancers for 2009 (I have only considered those with more than 200 deaths).  The percentages are the percentage of all the cancers listed.  The final column is the ratio of the numbers who died to the number of newly diagnosed.  This is not a proper measure of the likelihood of dying of the disease once it is diagnosed, but probably gives an impression of which are the more and which are the less deadly of the cancers.

Cancer Registrations and Deaths in New Zealand (2009: Ministry of Health, http://www.health.govt.nz/publication/cancer-new-registrations-and-deaths-2009)

Cancer Registrations and Deaths in New Zealand (2009: Ministry of Health, http://www.health.govt.nz/publication/cancer-new-registrations-and-deaths-2009)

The graph plots the percentages for new Diagnoses and deaths against the percentage of stories on the Stuff.co.nz web site for each of the cancers (ie relative to the total number of stories (20,757) for all these cancers.  I’m sorry to pick on Stuff, but it conveniently gave a count with a fast search engine.  The area above the dashed line (blue) suggests under reporting in the media, the area below over reporting.  Brain cancer is vastly over reported on this measure relative to other cancer death rates and new registrations.  Breast cancer is also over reported, particularly in relation to other cancer death rates.  Melanoma reporting reflects its deadliness, but not its new registrations.  Colorectal/Bowel cancer and Lung cancer are relatively poorly discussed compared to their relative death rates.

The percentage of new registrations and of deaths of various cancers against the percentage of stories in Stuff.co.nz.  Note, percentages are relative to the total number of new registrations/deaths/stories

The percentage of new registrations and of deaths of various cancers against the percentage of stories in Stuff.co.nz. Note, percentages are relative to the total number of new registrations/deaths/stories

There may well be many better ways to look at this kind of data – I would appreciate any suggestions.  I hope to look at other diseases as well.  However, as I research a disease that affects as many people as breast cancer each year, is just as deadly, and yet is reported on Stuff 1/50th as often, I am a little biased.

Tagged: brain cancer, breast cancer, cancer, lung cancer, media, melanoma

Nuclear war v Climate change John Pickering Dec 11

A nice little post by Peter Griffen on people preparing for doomsday reminded me of an ngram I generated a few weeks ago … we seem to talk as frequently about climate change now as we did nuclear war 25 years ago…ahhh, those were the days.

Frequency of appearance of the phrases "climate change" & "nuclear winter" in books written in English.

Frequency of appearance of the phrases “climate change” & “nuclear war” in books written in English.

Tagged: climate, climate change, doomsday, ngram, nuclear war

The minister missed the point John Pickering Dec 10

Last week Radio NZ put together a piece on grant funding.  The audio can be downloaded from here http://www.radionz.co.nz/national/programmes/morningreport/audio/2540317/scientists,-minister-at-odds-over-research-funding

Prof Juliet Gerrard, Dr Mark Green, Dr Robin Olds, Dr David Baddeley and myself all pointed out that the government grant funding system is in crisis because only 7-8% of applications are funded.  We also noted this made long science careers in this country almost impossible.  If I may add one other name, that of Sir Peter Gluckman, the government’s science advisor, who at a talk at the University of Otago Christchurch in 2009 called the time following the post-doctoral period of a scientists career as the “valley of the shadow.”  Many of today’s Professors went through that valley when there was considerably more light and less shadow.  Now, the shadows have grown long and dark and few make it through the valley.

Minister Joyce pointed out that we train twice as many science PhD’s as a few years ago and that most who go overseas “come back.”  I doubt the latter very much.  However, I am unable to find data on that.  What I did find was that the MOE themselves note the low rate of employment of PhD Natural and Physical Sciences PhD graduates.

“By field of study, graduates from ‘Natural and physical sciences’ had the lowest rate of employment [57%], while graduates from ‘Society and culture’ had the highest [65%]. Once again, this may reflect the limited employment opportunities for science researchers in New Zealand.”   (http://www.educationcounts.govt.nz/__data/assets/pdf_file/0019/104275/Do-People-with-Doctoral-Degrees-get-Jobs-in-NZ-Post-Study.pdf)

The research was based on those who graduated in 2003.  There were 199 students in this group in 2003 and 262 in 2010 (http://www.educationcounts.govt.nz/statistics/tertiary_education/research). I wonder what the rate of employment is?

Minister Joyce, as one would expect, pointed out all that the present government has done for science in this country.  To be fair, they have done more than other recent governments.  Minister Joyce repeatedly pointed to the increases in science funding for various schemes.  These amount to about a 24% increase in total science funding since 2009. ie about 5 to 6% per year.  This may be compared to a consumer price index increase of about 10% over 4 years.  In other words, total government spend on science has increased at faster than the rate of inflation. Minister Joyce called this dramatic.  I wouldn’t go this far, but it is positive and good.  In the Christhurch Press, Dec 1, in an article about Sir Peter Gluckmann. Sir David Skegg, president of the Royal Society, describes the government increase for science as “modest”  and notes that “the much needed step-change in our national investment in research and development has not yet occurred…”  I couldn’t agree more.  What is needed is not 5% a year, but 50%.

Innovation is but a fraction of the tip of the iceberg.  (Work by Uwe Kils) http://www.ecoscope.com/iceberg/

Innovation is but a fraction of the tip of the iceberg. (Work by Uwe Kils) http://www.ecoscope.com/iceberg/

A few other thoughts:

The metamorphosis of the Ministry of Research, Science and Technology into the Ministry of Business Innovation and Employment is symptomatic of a fundamental misunderstanding of both science and innovation.  Innovation for commercial gain is but a fraction of the visible fraction of the iceberg of science.  Innovation is built on decades of science in which the foundations are assembled molecule by molecule.  The results are a vast array of knowledge, largely freely accessible, which enables much social good and, yes, occasional commercial ventures.  The current pursuit of innovation innovation innovation threatens the very stability of the system.  If there are not scientists building the foundations, there will be little left for businesses to build on.

The grant funding system is broke.  It is time for politicians of all stripes to acknowledge that.  While additional funding is an essential element in saving our science, it is only part of the solution.  Fund scientists first, projects second.  To do otherwise is to commit the fallacy of picking winners in science – of trying to anticipate where science will be in 1, 2, 5 years.  It’s not possible and ignores that science is inherently unpredictable because it deals with what we don’t know, not with what we do.

Tagged: grants, Science, Stephen Joyce

The science funding story continues John Pickering Dec 01

Heads up.  A few weeks ago I posted about the crisis in grant funding in NZ.  This led to a number of discussions with a journalist from Radio New Zealand.  Laura Bootham has shown great persistance in tracking down facts and people.  I look forward to hearing what she has come up with. She tells me:
 ”The story on science funding airs on Monday around 7:20am but I recommend listening from 7:10am until 7:30am news as things are liable to change depending on what happens new-wise in the interim.”

Tagged: grants, meia, radio new zealand, Science funding

Hope for Type I diabetics John Pickering Nov 23

Living Cells Technology have announced the beginning of phase II trials of their product for helping Type I diabetics (they call it DIABECELL).  The idea behind the technology is to inject cells (called islet cells – normally present in the pancreas) that can sense glucose levels and release insulin.  LCT has managed to isolate these cells from pigs and encapsulate them in a way that the body’s immune system will not react to them – no anti-rejection drugs necessary.  Being xeno-transplant it has gone through quite a process even to get to the stage of Phase I trials.

This is pretty cool and I sure hope it all works out.  A Phase I/IIa (safety trials and first stage efficacy trial aimed to find an optimal dose) has been conducted at Middlemore hospital in New Zealand and another is underway in Argentina.  A press release in September announced the success of the Middlemore trial:

The New Zealand dose-finding trial was led by Dr John Baker at Middlemore Hospital in Auckland and saw 14 patients treated with a single implant of DIABECELL at doses of 5,000, 10,000, 15,000 and 20,000 IEQ/kg (islet equivalents per kilogram of body weight). The trial demonstrated that DIABECELL is a safe and effective treatment which results in: 

  • a statistically significant reduction in unaware hypoglycaemic events at doses of 5,000 and 10,000 IEQ/Kga
  • trend to reduction in HbA1c
  • improvement in patient-reported quality of life 

Note – HbA1c is just a form of haemoglobin (from the blood) proportional to the blood plasma glucose concentration.

Positive preliminary results from the 9 person Argentina based Phase I/IIb trial were announced.  The difference from the NZ trial is that two doses were given 12 weeks apart.  Followup has not been complete.

While this is all good news, I see no indication that the research has been peer reviewed (nothing in the Press release and I looked on PubMed as well).

The announcement this week is of a phase IIb trial of 20 patients with a dose of 10 IEQ/kg.  The announcement mentioned the trial will be in Argentina with 20 patients.  This is a little different from a September press release which mentioned 15 patients. The hope to metamorphosise the Phase IIb trial into a Phase III trial with an additional 10 patients from NZ.  A Phase III trial is to confirm effectiveness and monitor side effects – it is intended as the final step before regulatory approval.

In the press release the CEO announced.

“We remain on track to meet our goal of completing clinical trials of DIABECELL by 2015 and having a product commercially available by 2016.”

When I read this I thought “gulp – that is pretty positive given trials have yet to be completed.”  I gulped twice when I realized the trials to date have yet to be peer reviewed (although some results are public).  My third “gulp” is that these trials are all in small numbers – especially the planned Phase III trial.  That is not to say that I have any suspicions about the results or the technology, merely I worry about the juxtaposition of “completing clinical trials” and “commercially available” without the explicit interim statement of “and if the product is shown to be safe and effective.”

Tagged: Clinical trials, DIABECELL, insulin, islet cells, living cell technologies, porcine, Type I diabetes

Obama 91% Romney 9% John Pickering Nov 07

I published yesterday about my modeling showing Ricky Ponting’s last innings helps predicts the chance of Australia winning.  Today I came across the New York Times “538″ blog which uses a prediction model to predict Obama currently has a 91% chance of winning the Presidential Elections.  The reason it is so different from the polls which just report the percentage of people who say they will vote for one or other candidate is because in the US electoral system is all about winning the electoral college votes State by State. The “Chance of winning” model is put together by a bloke (Nate Silver) who rose to fame with his models to predict athlete’s performance.  His predictions use polling data, plus a regression analysis, projections and multiple simulations (see here).  Fascinating.

Tagged: Election, Modeling, New York Times, Obama, Prediction, Romney

Ponting’s last innings John Pickering Nov 06

“Only as good as your last match” goes the cliché.  This is true for Ricky Ponting and here is why. I recently published an article1 (Open Access :) ) on some new techniques being used in medical research which determine if making an additional measurement improves what we call “risk stratification.”  In other words – does measuring substance X help us to rule in or rule out if someone had a disease or not.  I got a bit board with talking about “biomarkers” and medical stuff, so when it came to presenting this at the Australian New Zealand Society of Nephrology’s annual conference I looked to answer the very important question: “Does Ricky Ponting’s last inning’s matter?”, or in Australian cricket jargon “Ponting, humph, he’s only as good as his last innings, mate.”

How did I do it?

  1. I chose Australia winning a one-day international when chasing runs as an outcome (Win or Loss).
  2. Using data available from Cricinfo I determined which of the following on its own predicts if Australia will win (ie which predicts the outcome better than just flipping a coin): (1) Who won the toss, (2) whether it is a day or night match, (3) whether it is a home or away match, (4) how many runs the opposition scored.
  3. As it turned out if Australia lost the toss they were more likely to win (!), and, not surprisingly, the fewer runs the opposition scored the more likely they were to win.  I then built a mathematical model.  All this means is that I came up with an equation where the inputs were the winning or losing of the toss and the number of runs and the output was the probability of winning.  This is called a “reference model.”
  4.  I added to this model Ricky Ponting’s last innings score and recalculatd the probability of Australia winning.
  5. I then could calculate some numbers which told me that by adding Ricky Ponting’s last innings to the model I improved the model’s ability to predict a win and to predict a loss.  Below is a graph which I came up with to illustrate this.  I call this a Risk Assessment Plot.

So, when the shrimp hit the barbie, the beers are in the esky, and your mate sends down a flipper you can smack him over the fence for you now know that when Ricky Ponting scored well in his last innings, Australia are more likely to win.

The middle bit is the Risk Assessment Plot. The dotted lines tell us about the reference model. The solid lines tell us about the reference model + Ricky Ponting. The further apart the red and blue lines are the better. The red lines are derived from when Australia won, the blue lines from when the lost. If you follow the black lines with arrows you can see that by adding in Rick Ponting’s last innings the model the predicted probability (risk) of a win increases when Australia went on to win (a perfect model would have all these predictions equal to 1). Similarly the predicted probability of a loss gets smaller when Australia did lose (ideally all these predictions would equal 0).

  1. Pickering JW, Endre ZH. New Metrics for Assessing Diagnostic Potential of Candidate Biomarkers. Clin J Am Soc Nephro 2012;7:1355–64.

Tagged: Australia, australian cricket, Biomarkers, cricinfo, Cricket, innings, last match, one-day, Ricky Ponting, Risk Assessment Plot, risk stratification, sports, Statistics

Congratulations awardees – shame on the system John Pickering Oct 25

At 1am this morning (has someone something to hide?) the recipients of Marsden grants were announced.

Congratulations to them all.

$54.6 million was distributed over 86 research projects.  Marsden funds “blue skies” research across a number of disciplines – humanities, science, technology etc. The list of topics reflect the diversity.  I think that they are worth celebrating so I have listed below the projects and awardees mentioned in the media pack (only 30 something, so there must be others).

The awards fall into two categories:  Standard grants of up to $330K per annum for three years (open to anyone) and Fast-start grants of $115K per annum for three years which go to early career researchers (within 7 years of getting PhD:  It used to be 7 years of post PhD research experience which enabled me to get such a grant 3 years ago despite having had a 15 yr hiatus between postdoc and next science position – they changed the rules the following year!).

Shame on the system

While 86 projects were funded, 1113 proposals were made.  This is a success rate of 7.7%.  I have posted before on just what such an appalling low success rate looks like when the Health Research Council funded just 7% of proposals.  This is a crisis.  Successive governments are responsible.  Fellow sciblog bloggers Grant Jacobs and Eric Campton pointed out to me Canadian research which showed the total cost to prepare grant proposals was greater than the amount awarded.  Eric blogged about this in 2009.  When is/was the cross-over point for HRC or Marsden funding?  Was it when the success rate fell below 20% (crisis point according to HRC chief executive Robin Olds).  Is it still viable at 7%.  Minister Steven Joyce needs to put some people onto answering that question straight away.

Colleagues of mine have talked about Marsden and HRC becoming a lottery.  They are not taking away from the tremendous work and great insights grant recipients have shown, only that many others have also shown those attributes without getting funding.  The problem is having to rank a large bunch or excellent applications.  This is not “taking the cream off the top”, rather it is attempting to pick out the tastiest tiny fraction of the cream – an impossible and meaningless task.  Perhaps this is why in announcing the new Explorer grants the Health Research Council have said that any proposals that meet the criteria will go into a pot and the grantees will be decided by lottery.  Quite possibly this may be just as fair as a ranking system.  Quite probably the HRC have been driven to this position because of the unwillingness of researchers to sit on committees and spend many hours shuffling paper making impossible ranking decisions knowing that such a small proportion of applicants will be funded.

(ps – please forget I mentioned the Explorer grants…I may apply for one myself, and I don’t want too many people knowing about it as this will reduce my chances).

The Projects

Ozone’s role in Southern Hemisphere climate change
Dr Olaf Morgenstern
NIWA
 
Searching for the tell-tale signs of galaxy cluster formation.
Dr Melanie Johnston-Hollitt
Victoria University of Wellington
 
Earthquake hydrology gets a shake up
Dr Simon Cox
GNS Science
 
Clarity vs efficiency in speech
Dr Donald Derrick
University of Canterbury
 
Gesture, speech, and the lopsided brain. 
Professor Michael Corballis
University of Auckland
 
Dem bones, dem bones, dem … heavy bones. 
Professor Stephen Robertson
University of Otago
 
Young cancer researchers get funding boost 
Dr Anita Dunbier and Dr Zimei Wu
Dunbier: University of Otago, Wu: University of Auckland
 
Kauri and climate change. 
Dr Catriona MacInnis-Ng
University of Auckland
 
How do birds “tell the time” when migrating?
Dr Phil Battley
Massey University
 
Unravelling male reproductive responses to social cues. 
Dr Patrice Rosengrave
University of Otago
 
Pollen key to plant development  
Dr Lynette Brownfield
University of Otago
 
How does the heart grow?
 Professor Peter Hunter
The University of Auckland
 
Getting to the heart of heart failure
 Professor Martyn Nash
The University of Auckland
 
Could tidal power realistically help meet future energy needs?
Dr Ross Vennell
University of Otago
 
Making a controlled splash. 
Dr Geoff Willmott
Industrial Research Limited
 
Getting to the heart of dark matter 
Dr Brendon Brewer
The University of Auckland
 
Criminal minds – the science behind the science
Dr Heather Wolffram
University of Canterbury
 
Toi Te Mana: A history of indigenous art 
Dr Deidre Brown
The University of Auckland
 
Cloaked in invisible bending light
Dr Robert Thompson
University of Otago
 
Laughing gas not so funny on high
Dr Joseph Lane
The University of Waikato
 
New Zealand Agribusiness investing in rural China
Dr Jason Young
Victoria University of Wellington
 
Converting microwave photons to optical photons
Dr Jevon Longdell
University of Otago
 
Identity and wellbeing in Aotearoa New Zealand.
Associate Professor Helen Moewaka-Barnes
Massey University
 
Corporate community development: harnessing business power in the Pacific. 
Professor Regina Scheyvens
Massey University

Tagged: grants, Health research council, Marsden, Steven Joyce

Helmetless bike riders – a dying breed John Pickering Oct 24

A few weeks ago a member of Christchurch City Council and Canterbury District Health Board advocated the non-wearing of bike helmets.  I commented on the idiocy of this at the time. A source tells me that said person got a hard time from other CDHB board members-good.

Perhaps this recent research will put the anti-establishmet hair-brained non-conformists back in their box.  According to Canadian researchers those not-wearing helmets are three times more likely to die in a road accident than those wearing helmets. Their interpretation of the results is simple:

“Not wearing a helmet while cycling is associated with an increased risk of sustaining a fatal head injury.”

Tagged: bicycle, bike, CDHB, cycle, head injury, helmets, safety

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