The ISBGroup Blog

In the last week, we arranged a 2-day workshop on Biomedical engineering and decision-support. This workshop featured around 20 speakers and 30 attendees, from a wide variety of backgrounds. These backgrounds include all the steps involved in creation of decision-support systems (new biosensors, patient and personal health records, mathematical models, and the creation of usable interfaces), the testing and implementation of such systems (user-experience and user-groups, social scientists, health economy, implementation science, service design, and clinical end-users), and people from medical pedagogics, companies, and clinical decision-makers. This workshop was intended as a step towards further advancing the second-round of three already submitted VINNOVA applications (still pending), and – more generally – as a step towards the creation of a Linköping-based centre on Biomedical engineering and decision-support. This endeavor is open, so if you are interested in this process, send an email to either of the two arrangers: Elisabet or Gunnar Cedersund (elisabet.cedersund@liu.se and gunnar.cedersund@liu.se)

Some more information can be found at the workshop home page.

We have had an abstract selected for an oral
presentation at the 6th Conference
on Systems Biology of Mammalian Cells in Munich. The abstract is about our
long-term work with diabetes modeling. Gunnar will hold the presentation April
8th in the session Systems Medicine &
Systems Pharmacology chaired by Werner Mewes & Frank
Lammert. We hope to see you there!

On June 1, our annual project course – the Bachelor’s course for the ~30 students in Engineering Biology, TBMT33 – is having its final presentation day. This is a good chance to get a quick overview of existing projects within ISBgroup, and to see some of the different ways that mathematical modelling can be used as an integrated tool in experimental and clinical research. The schedule of the day is as follows.

All presentations in Linden, Campus US
8.15-9: Master Thesis presentation, “Quantitative translation of drugs’ effects on type 2 diabetes mellitus: from diabetic rodent models to patients”, Philip Blomström. Supervisors: Elin Nyman and Monika Sundqvist, Project done at AstraZeneca

9.15-9.45 “Intracellular insulin signalling and mechanisms of adiponectin release”. Supervisor: Rasmus Magnusson. Collaborating groups: Peter Strålfors (IKE), Cecilia Brännmark (Gothenburg Univ).
9.45-10.15 “Improvement of a Mathematical Liver Model for Diagnosis and Surgical Planning”, Supervisor: Markus Karlsson. Collaborating group: Peter Lundberg (IMH/CMIV)

10.15-10.30 Break

10.15-10.45 “Multi-level and multi-time scale modelling of glucose homeostasis disorders: monitoring in ICU and obesity drug simulations”
Supervisor: Andrea Hjelm. Collaborating groups: Peter Strålfors (IKE), Peter Gennemark (AstraZeneca), Folke Sjöberg (IKE)

10.45-11.15 “Modelling the BOLD response in fMRI”
Supervisor: Karin Lundengård. Collaborating group: Maria Engström (IMH/CMIV), Fredrik Elinder (IKE)

11.15-11.45 “Understanding desensitization – by examining cardiac myocytes and sensory neurons”
Supervisors: William Lövfors and Rikard Johansson. Collaborating groups: Jordi Altimiras (IFM), Claudio Altafini (ISY)

12-13 Poster presentations of all projects outside of Berzelius.

Questions and more info: Gunnar Cedersund, gunnar.cedersund@liu.se

Welcome! 🙂

On Thursday and Friday, the 6th Swedish Meeting on Mathematics in Biology takes place in Linköping.

We will be there and do a small presentation of our work. Hope to see you there!

Karin Lundengård just did her half-time, and it’s on youtube!

“My research project is on the activity of the human brain. The activity can be measured by functional Magnetic Resonance Imaging, which measures the Blood Oxygen Level Dependent (BOLD) response. As the name states, it is the oxygen levels being measured, but they are connected to the electrical signaling of the neurons via the neurovascular coupling. There are several hypothesis about the underlying mechanisms of the neurovascular coupling and here we have used mechanistic dynamic models to investigate two of them. So go have a look at the video to see how it went!”

Hopefully the article will be submitted for press before Christmas.

Karin Lundengård
PhD student at IMH and CMIV

Can anything be nicer than combining work with a trip to
Norway? – Probably, the pizza was as expensive as the myths foretold.

Joking aside, during the field trip to the conference
Virtual Physiological Human in Trondheim, a summit to discuss multi-level
models representing human physiology, the ISB group once again got a chance to
display its work. With the help of several presentations, both oral and
posters, new contacts were made and there was much rejoicing!

As a student visiting such an event for the first time, one
cannot help but feel a bit lost among the field leaders and other experts. I
can also admit that I was pretty nervous about my own poster presentation, but I
started to relax some time into the poster session.

To sum up the trip: Making new connections and getting out
our research is enjoyable, eating pizza in Norway, not so much.

Right before christmas, Linnea Bergenholm presented her master thesis Modeling as a Tool to Support Self-Management of Type 1 Diabetes. This thesis work was done in our group, collaborating with the companies Linkura and Wolfram Mathcore, aiming to develop and investigate dosing tools for diabetics.

You can download the thesis here

Abstract:

Type
1 diabetes (T1D) is an auto-immune disease characterized by
insulin-deficiency. Insulin is a metabolic hormone that is involved in
lowering blood glucose (BG) levels in order to control BG level to a
tight range. In T1D this glycemic control is lost, causing chronic
hyperglycemia (excess glucose in blood stream). Chronic hyperglycemia
damages vital tissues. Therefore, glycemic control must be restored.

A
common therapy for restoring glycemic control is intensive insulin
therapy, where the missing insulin is replaced with regular insulin
injections. When dosing this compensatory insulin many factors that
affect glucose metabolism must be considered. Linkura is a company that
has developed tools for monitoring the most important factors, which are
meals and exercise. In the Linkura meal and exercise tools, the
nutrition content in meals and the calorie consumption during exercise
are estimated. Another tool designed to aid control of BG is the bolus
calculator. Bolus calculators use input of BG level, carbohydrate
intake, and insulin history to estimate insulin need. The accuracy of
these insulin bolus calculations suffer from two problems. First, errors
occur when users inaccurately estimate the carbohydrate content in
meals. Second, exercise is not included in bolus calculations. To reduce
these problems, it was suggested that the Linkura web tools could be
utilized in combination with a bolus calculator.

For this purpose,
a bolus calculator was developed. The bolus calculator was based on
existing models that utilize clinical parameters to relate changes in BG
levels to meals, insulin, and exercise stimulations. The bolus
calculator was evaluated using data collected from Linkura’s web tools.
The collected data showed some inconsistencies which cannot be explained
by any model. The performance of the bolus calculator in predicting BG
levels using general equations to derive the clinical parameters was
inadequate. Performance was increased by adopting an update-algorithm
where the clinical parameters were updated daily using previous data.
Still, better model performance is prefered for use in a bolus
calculator.

The results show potential in developing bolus
calculator tools combined with the Linkura tools. For such bolus
calculator, further evaluation on modeling long-term exercise and
additional safety features minimizing risk of hypoglycemia are required.

Today Zaheer Ali, who has been working in our group since spring 2012, presented and defended his work.

The title was Mathematical Modeling of Electrophysiological Data of Facilitation in Layer 6 Pyramidal Cells (abstract below).

Abstract:

Facilitation is a distinctive activation pattern shown by pyramidal
cells in the layer 6 of the cerebral cortex upon rapid and repeated stimulations.
This behavior leads to the generation of tonic-clonic seizures which is a
defining feature of epilepsy. Patch-clamp recording techniques performed on
these cells show facilitation in different experiments. A mathematical modeling
approach is used in order to find the possible mechanism of facilitation
depending on different calcium domains in the presynaptic neurons. Four
different versions of the model have been constructed using ODEs. First version
of the model is a simple model of three compartments in the presynaptic neuron
with an influx of calcium at the triggering calcium compartment, the buffer
compartment and the stable internal domain of calcium can describe the data of
facilitation. Second version of the model has the calcium influx through a
micro-domain compartment near the cell membrane because of physical distance
between ion channel and the vesicle, in addition to the three compartments. The
third version of the model has a limited calcium buffer without micro-domain
calcium compartment which provides saturation to the buffer in this model and
the final version of the model is similar to third version of the model with
the addition of a micro-domain calcium influx. All models can describe the
experimental data sets of facilitation separately fitted to the model. In
addition, the third version of the model can describe all the experimental data
at the same time qualitatively.