<div dir="ltr"><div>Daer Pedro,<br><br></div>thank you for your entertaining way of presenting my Sisyphus theme about medicine in a nutshell, which was mostly enjoyable to read. Actually, you are right, medicine is "messy", which qualifies it more like a liberal art discipline rather than science, full of workshop type of hustle and bustle, ad hoc insights of mystic adepts followed by faithful scholars and mixed with cutting edge technology wherever possible (in the Western world). It appears that every effort to organize it in the manner we know in mathematics and physics is doomed to failure. I realise that the subject's depth reflected in my presentation is indeed overwhelming. Yet, it was not my intention to put a Sisyphus rock upon this forum. Thank you for your and Koichiro's simplified pedestrian analysis of the theme. We can go with thes rephrased set of questions further. <br><div><div><div><div class="gmail_signature"><div dir="ltr"><div><div dir="ltr"><div><div dir="ltr"><div><div dir="ltr"><div><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div dir="ltr"><div><br></div></div></div></div></div></div></div></div></div></div></div></div></div></div></div><div class="gmail_extra">
<br><div class="gmail_quote">On Tue, May 17, 2016 at 12:51 PM, Pedro C. Marijuan <span dir="ltr"><<a href="mailto:pcmarijuan.iacs@aragon.es" target="_blank">pcmarijuan.iacs@aragon.es</a>></span> wrote:<br><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex">
<div bgcolor="#FFFFFF" text="#000000">
<div>Dear Plamen,<br>
<br>
Thanks for the synthetic attempt. You have put together pretty
complex strands of thought that become too demanding for a general
response. I will concentrate in a few points.<br>
<br>
What is Medicine? In what extent is it amenable to "integration"?
Is reductionism an anathema in medicine? Can we regularly ascend
from cellular info flows to organs/systems, and to healthy
individuals/environments? <br>
<br></div></div></blockquote><div><br></div><div>These are good general questions, but I'd rather wish to focus on one specific problem, e.g. the one of the metastatic melanoma that Koichiro addressed in his example and try to "dissect" it as in the article in his example. It is clear to me that I cannot focus on one single thing and brainstorm on it all the time. But the idea behind this concluding workshop was to be less philosophical and more practical in trying to investigate if we can reshape medicine as an extension of biology. After all, huge amounts of money are given for research here, more than in any other field, as far as I know. Are these investments justifyable in the way this "engineering science" is performing today? Is there anything that could make this discipline more predictable, at least at the curruculum level?<br> <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>
The history of Medicine shows messiness in the highest degree. To
note that it was not included in the Trivium/Quadrivium medieval
scheme of knowledge, and was only accepted within the "mechanical
arts" after Hugh of St. Victor compilation (XIII Century), many
decades after the first Faculties of Medicine were created in
Italy. Why medicine is so messy? Just go the wiki pages on the
topic: hundreds of subspecialties are listed, and under all those
terms we imply all the internal and external ("natural") phenomena
that can derail and put out of track the advancement of a life
cycle. Each one of those specialties has to arrange its own world
of knowledge, with lots of analytical and synthetic avenues not
amenable to neat overall schemes and to formal approaches except
in some reduced pockets. Successful reductionist strategies and
analytical techniques are piled up with holistic views, and reams
of tacit knowledge (indeed medicine is a very stratified small
world of "lords", "masters", "disciples", "servants", and
"beginners").<br></div></div></blockquote><div><br></div><div>This is all true. But it is also true that medicine has been always very important for us human beings.<br> <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>
<br>
So, like in engineering, one has to be suspicious of far reaching
implications for the term "integrative". Not necessarily in this
case with the "3φ" connotation. </div></div></blockquote><div><br></div><div>Indeed, there coud be a "3φ", a "4φ", or a "3φ+ 1<span style="font-size:12pt;font-family:Symbol"><span style="mso-list:Ignore"><span style="font:7pt "Times New Roman""></span></span></span><span style="font-size:10pt;font-family:"Arial",sans-serif" lang="EN-US">ψ", ... etc. Greek alphabet built polynomial connotations encoded in this prefix. The question is wether we can use such kind of combination from the known natural science disciplines and extend them by some humanitarian fields in order to address key issues in an organised and diligent manner in medicine. We know well that there are both serios conflicts between some branches and efforts to reconcile them. The prefix I used was to make clear that we are asking for a novel kind of integration, if possible. Yet this prefix definition should not be considered "fixed" once for ever. <br><br></span><span style="font-size:12pt;font-family:"Times New Roman",serif"></span>
</div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>But the strong reliance on
criticality could be subject to scrutiny. Quite many cellular /
biomolecular phenomena do not especially rely on criticality
--perhaps the most essential ones, related to "codes", genomic
maintenance, protein synthesis, protein degradation, signaling,
apoptosis, etc. Why the integrative strategy should rely on a term
that notwithstanding strong physical grounds, has relatively thin
explanatory capability in the biological? </div></div></blockquote><div><br></div><div>Criticality is a phenomenon that holds both for living and non-living matter. This is something that "matters". Of course, one could take "autopoiesis" instead, which is also a good choice. I am not sure how far we can go with this this "criticality" bus. I had to start somewhere my talk, and I made this choice to facilitate the transition to medicine. If anyone has a better suggestion, I do not mind. <br> <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>It is a long story of
looking for responses "where the physical/math light is" and not
where the biol. problems are. <br>
<br></div></div></blockquote><div><br></div><div>I agree. This is the real issue. How can "<span style="font-size:12pt;font-family:"Times New Roman",serif;color:rgb(136,136,136)"></span>"3φ", "4φ", or "3φ+ 1<span style="font-size:12pt;font-family:Symbol"><span style="mso-list:Ignore"><span style="font:7pt "Times New Roman""></span></span></span><span style="font-size:10pt;font-family:"Arial",sans-serif" lang="EN-US">ψ + </span><span style="background-color:rgb(255,255,255)"><span style="font-size:10pt;font-family:"Arial",sans-serif" lang="EN-US"></span><span style="color:rgb(0,0,0)"><span style="font-size:12pt;font-family:"Times New Roman",serif">µ</span><span style="font-size:10pt;font-family:"Arial",sans-serif" lang="EN-US"></span></span></span>
<span style="font-size:10pt;font-family:"Arial",sans-serif" lang="EN-US">" help us is the question.<br><br></span> </div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>
My view, I can be wrong but I have worked considerably on the
matter, is that cellular signaling, the crisscrossing of info
flows that provide the singular intelligence and adaptability of
organisms, is not well articulated yet. Neither in evo-devo, nor
in physiology, medicine and health. In this regard all the present
parlance on information processing that accompanies the tremendous
technological info-tech revolution does not represent a help,
maybe the opposite. </div></div></blockquote><div><br></div><div>Unfortunately, you appear to be right. I am also not convinced that Big Data is blessing rather than a curse.<br> <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>The deep info problems are taken as already
solved and articulated synthesis are undertaken as mere
agglutinations. Maybe the problem is too deeply complex, and
medicine is as always too messy.<br></div></div></blockquote><div><br></div><div>The question we could try to answer here is: can we do something to disentangle the spaghetti dish of medicine? <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>
<br>
Sorry if seemingly I have joined the "Cassandra" club!<br></div></div></blockquote><div><br></div><div>I don't think so. Yours are fair concerns.<br><br></div><div>Best,<br><br></div><div>Plamen<br><br></div><div> <br></div><blockquote class="gmail_quote" style="margin:0px 0px 0px 0.8ex;border-left:1px solid rgb(204,204,204);padding-left:1ex"><div bgcolor="#FFFFFF" text="#000000"><div>
Best--Pedro<div><div class="h5"><font size="+2"><br>
<br>
<br>
<br>
</font>El 14/05/2016 a las 9:49, Dr. Plamen L. Simeonov escribió:<br>
</div></div></div><div><div class="h5">
<blockquote type="cite">
<div dir="ltr">
<div><span style="font-family:Arial;font-size:10pt">Dear
Colleagues,</span><br>
</div>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">My
contribution will
finalize the discussion on phenomenology in the domains of
biology,
mathematics, cyber/biosemiotics and physics by the previous
speakers (Maxine,
Lou, Sœren and Alex) with a “challenging topic” in <u>3φ
integrative medicine</u>.
<b>You may wish to skip the small font text
notes following each underscored phrase like the one
below.</b></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><u><span style="font-size:8pt;font-family:Arial" lang="EN-US">Note
1:</span></u><span style="font-size:8pt;font-family:Arial" lang="EN-US"> Although this term is often
used as synonym for holistic healing (s. ref. list A), its
meaning in this
context with the prefix 3φ goes much “deeper” into the
disciplines’ integration
leaving no room for speculations by mainstream scientists.
The concept is a
linguistic choice of mine for the intended merge of the
complexity sciences <u>ph</u>ysics
and <u>ph</u>ysiology with <u>ph</u>enomenology for
application in modern medicine
along the line of integral biomathics (s. ref. list B). </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">It is
rooted in the last presentation
of Alex Hankey, since it naturally provides the link from
physics to physiology
and medicine, and thus to an anthropocentric domain implying
a leading part of
phenomenological studies. To begin, I compiled a précis of
Alex’ thesis about
self-organized criticality (s. ref. list C) from his paper
“A New Approach to
Biology and Medicine” -- the download link to it was
distributed in a previous
email of him -- and extended it with my reflections
including some questions I
hope you will resonate on. </span></p>
<p class="MsoNormal" style="text-align:justify"><br>
</p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">I am
curious of your
opinion about how to apply the scientific method, and in
particular mathematics
and information science, to study illness and recovery as
complex phenomena. </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Alex
Hankey: self-organized criticality and regulation in
living systems</span></b></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">There
is a continuous growth and change
at the end of a phase transition in an organism, i.e. at
its critical point,
which is the end point of phase equilibrium.</span></b></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Both
endo and exo, genetics and
epigenetics are important for life.</span></b></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Self-organized
criticality</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> is a
characteristic
state of a system at its critical point generated by
self-organization during a
long transient period at the complexity edge between
order/stability/predictability
and disorder/chaos/unpredictability.</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><i><span style="font-size:10pt;font-family:Arial" lang="EN-US">Regulation
of growth, form and function as a balance between
health and illness.</span></i></b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> The
role of regulation and homeostasis in maintaining the
structure
and function of living systems is critical. Every deviation
from a regulated
state of being leads to imbalances, failures and subsystem
dysfunction that is
usually transitory, but could also become life-threatening,
if the organism
cannot find a way to restore quickly to a balanced, healthy
state. Living
beings are robust and fault-tolerant with respect to
hazards; they possess multiple
alternative pathways for supplying and maintaining their
existential functions.
However, some state transitions in response to severe harms
can become practically
irreversible, because of the deep evolutionary interlocking
between the
participating entities and processes. Sometimes the normal
functioning of the organism
cannot be easily restored by its natural repair processes,
especially when adversities
reoccur frequently, and the organism fails ill.</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Synchronicity
of action and
information between the building blocks of a living
system.</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> There
is a need for
every physiological function to be correctly coordinated
with all other “peer” functions.
Information flows within a living system interconnect all
physiological functions
and organs at multiple levels into a single mesh of
regulatory
interconnections. Multiple feedback-control loops enable the
cross-functional
interlocking of both healthy and ill state changes of the
organism. Adjacent/peripheral/secondary
homeostasis processes act as fine-tuning catalyzers of
substrate ratios and
process rates exchanged within the living system. Imbalances
of these
quantities lead to excess/blockage or scarcity/draining of
essential
nourishment and information exchange pathways.</span></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<p class="MsoNormal" style="margin-left:36pt;text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Regulation
at criticality</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> not
only fine-tunes a
process, it <i>optimizes</i> it for
survival: with respect to a given generation’s available
possibilities in the
light of the past generations’ possibilities. To survive an
organism or a
species needs to develop optimal <i>response-ability</i>
to environmental distress.</span></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"><br>
</span></b></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">New
ecological definition of life according to Hankey:
self-regulating,
self-reproducing systems that maximize efficiency of
function to maximize competitiveness
in their chosen environment. </span></b></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">Summary:
Elements of self-organized criticality</span></b></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<ol style="margin-top:0cm" start="1" type="1">
<li class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Criticality</span></li>
<li class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Edge
of the chaos</span></li>
<li class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Self-organized
criticality</span></li>
<li class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">1/f
fractal patterns of response </span></li>
</ol>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">…
and beyond</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US"></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">I wish
to add a 5<sup>th</sup>
aspect to this definition from the perspective of integral
biomathics:</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<ol style="margin-top:0cm" start="5" type="1">
<li class="MsoNormal" style="text-align:justify"><i><span style="font-size:10pt;font-family:Arial" lang="EN-US">Phenomenology</span></i></li>
</ol>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial;color:red" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">The
latter is a largely
studied matter in contemporary medicine (s. ref. list D), at
least at the
macro, interpersonal <u>level</u>. </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal"><u><span style="font-size:8pt;font-family:Arial" lang="EN-US">Note
2</span></u><span style="font-size:8pt;font-family:Arial" lang="EN-US">: </span><span style="font-size:8pt;font-family:Arial;color:black" lang="EN-US">A level refers to the compositional
hierarchy defining levels by scale.</span><span style="font-size:8pt;font-family:Arial" lang="EN-US"></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">The
key question in such a “deep holistic”
physically-phenomenological
physiology (</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US">3φ<u>)</u><b>
is how to define or
comprehend (self-organized) criticality operationally
within the unifying framework
of biomathematics and biocomputation</b>. Indeed, a single
temporary imbalance within
a living system regarded as disease involves multiple
agents, perspectives and
interpretations at all levels altogether, moreover <u>simultaneously</u>.
</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><u><span style="font-size:8pt;font-family:Arial" lang="EN-US">Note
3</span></u><span style="font-size:8pt;font-family:Arial" lang="EN-US">: </span><span style="font-size:8pt;font-family:Arial;color:black" lang="EN-US">Simultaneously at different levels
involves very different sized 'moments' at the different
scales.</span><span style="font-size:8pt;font-family:Arial" lang="EN-US"></span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">So,
how should we
approach and take into account the other levels/scales in
order to derive a
reliable diagnosis and <u>therapy</u>? </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><u><span style="font-size:8pt;font-family:Arial" lang="EN-US">Note
4</span></u><span style="font-size:8pt;font-family:Arial" lang="EN-US">: </span><span style="font-size:8pt;font-family:Arial" lang="EN-US">The
notion of
“subject” becomes plural (“subjects”) as superposition of
quantum states to survive
the integration of the multiple first-person subjective
descriptions and the
standard third-person objective one. </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Until
now criticality has
been <u>non-phenomenological</u>. </span></p>
<p class="MsoNormal" style="text-align:justify"><br>
</p>
<p style="text-align:justify"><u><span style="font-size:8pt;font-family:Arial" lang="EN-US">Note
5:</span></u><span style="font-size:8pt;font-family:Arial" lang="EN-US"> In their 2012 paper “No
entailing laws, but enablement in the evolution of the
biosphere” Longo,
Montévil and Kauffman claim that biological evolution “marks
the end of a
physics world view of law entailed dynamics” (<a href="http://arxiv.org/abs/1201.2069" target="_blank"></a><a href="http://arxiv.org/abs/1201.2069" target="_blank">http://arxiv.org/abs/1201.2069</a>).
They
argue that the evolutionary phase space or space of
possibilities constituted
of interactions between organisms, biological niches and
ecosystems is “ever
changing, intrinsically indeterminate and even
(mathematically)
unprestatable”.Hence, the authors' claim that it is
impossible to know “ahead
of time the 'niches' which constitute the boundary
conditions on selection” in
order to formulate laws of motion for evolution. They call
this effect “radical
emergence”, from life to life. Yet this applies to abiotic
dissipative
structures like tornadoes as well. Living beings are not
radically different in
this respect. In their study of biological evolution, Longo
and colleagues
carried close comparisons with physics. They investigated
the mathematical
constructions of phase spaces and the role of symmetries as
invariant
preserving transformations, and introduced the notion of
“enablement” to
restrict causal analyses to Batesonian differential cases
(1972: “the
difference that makes a difference”). The authors have shown
that mutations or
other “causal differences” at the core of evolution enable
the establishment of
non-conservation principles, in contrast to physical
dynamics, which is largely
based on conservation principles as symmetries. Their new
notion of “extended
criticality” also helps to understand the distinctiveness of
the living state
of matter when compared to the non-animal one. However,
their approach to both
physics and biology is also <i>non-phenomenological</i>.
The possibility for endo states that can trigger the
“(genetic/epigenetic)
switches of mutation” has not been examined in their model.
This is intended to
be different in 3φ<i> integrative medicine</i>. </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">If we
split a human body
into macro (patient), mezzo (systems) and micro levels
(cells) three distinct
questions regarding phenomenology arise: i) <i>how</i>
these levels pervade into each other with </span><span style="font-size:10pt;font-family:Arial;color:black" lang="EN-US">larger scale providing context (boundary
conditions) and lowest scale providing raw materials for
middle scale to
function,</span><span style="font-size:10pt;font-family:Arial" lang="EN-US">
monitor
and control vital processes, ii) <i>who/which</i>
are the agents taking care for this to happen spontaneously,
and iii) <i>what kind and role</i> plays information in
the context of i) and ii). After all w<span style="color:rgb(26,26,26)">hat we are concerned
about is modeling the agency of the systems in the mezzo
level.</span> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial;color:red" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Where
should we go from
here?</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"><br>
</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">In
particular, I am
interested to know <b>what kind of <i>scientific-phenomenological
methodology</i>
can be developed and applied for investigating </b>the
following three major groups
of ailments:</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<ol style="margin-top:0cm" start="1" type="1">
<li class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">oncological
diseases</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US">
with a particular focus on spatial and temporal
heterogeneity both in terms of flawed histological
structures and biochemical reactions;</span></li>
</ol>
<ol style="margin-top:0cm" start="2" type="1">
<li class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">neuro-degenerative
disorders</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US">
such as vascular dementia, Parkinson and Alzheimer
diseases:</span></li>
</ol>
<ol style="margin-top:0cm" start="3" type="1">
<li class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">altered
organ and physiological system failures</span></b><span style="font-size:10pt;font-family:Arial" lang="EN-US">
such as the Multiple Organ Dysfunction Syndrome (MODS),
cardiovascular and autoimmune diseases.</span></li>
</ol>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial;color:red" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial;color:rgb(26,26,26)" lang="EN-US">In the first
group, the <b>extreme diversity of cancer
tissue structures and circulating tumor cells (CTC)
concentrations over both
spatial and temporal scales</b> makes the reliable
classification, diagnosis,
model/hypothesis generation, forecast and treatment of
individual patients very
difficult. This is a real challenge for modern pathology.
Another problem is
that pathologists are actually dealing with random tissue
and blood samples
over irregular periods, which hinder the exact 3D
histological reconstruction
of the tumor formations and tracing their development over
time and space.
Using additional means such as diagnostic sonography, CT,
MRT and PET images do
not improve sufficiently the hypotheses about the individual
cancer morphology
and development. All this makes tumor classification and
diagnosis, even when
analyzing high-resolution digital images from biopsy slices
by means of virtual
microscopy, very difficult and often a guesswork also for
experts. The recent
advances in high-performance medical scanning and automation
systems,
computerized visualization and graphical modeling tools, as
well the collection
of huge amounts of anonymous patient data in specialized
medical databases make
the impression that the solution of these problems is only a
question of more
automation, performance, investment and time. However, many
pathologists begin
to realize a third problem, namely that <b>tumors
appear to be <i>unique</i> in their
histological structure and development</b>, related to the
personal history and
the overall state of health of the individual patients. This
argument reveals
the need for developing a more personalized and
differentiated medicine that
goes over scales without becoming purely symptomatic,
causality-driven and
reductionistic.</span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Recent
research in the other
two fields leads to the same conclusion. Therefore, I think
that we may be able
to develop and test hypotheses about emergence and
development of deficiency
and illness that will lead to individual therapies in <i>3φ</i>
integrative medicine. Your ideas regarding this assumption
are
very welcome. </span></p>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="text-align:justify"><span style="font-size:10pt;font-family:Arial" lang="EN-US">Some
interesting
questions bridging the previous discussion sessions to this
one are: </span></p>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:10pt;font-family:Arial" lang="EN-US">-<span>
</span></span><span style="font-size:10pt;font-family:Arial" lang="EN-US">Why does a human embryo repeat the evolutionary
history of
its species when going through its development stages? Is it
because it is more
secure to project and set up the execution of a future life
plan by tracing and
bodily memorizing a series of evolutionary encoded
(successful) “locks” through
equilibrium states at the edge of criticality? </span></p>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:10pt;font-family:Arial" lang="EN-US">-<span>
</span></span><span style="font-size:10pt;font-family:Arial" lang="EN-US">Which is the <i>vital </i>role
of recursion and repetition of life processes including
their material and
information exchange flows in the criticality driven
self-regulation for
recovery from imbalances and the reversibility and healing
of diseases? How can
we effectively model such processes?</span></p>
<p style="margin-left:36pt"><span style="font-size:10pt;font-family:Arial" lang="EN-US">-<span>
</span></span><span style="font-size:10pt;font-family:Arial" lang="EN-US">Do we make difference between a
physicist’s time and a biologist’s time in complex living
systems?</span></p>
<p class="MsoNormal"><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> I
look forward to your feedback and notes on the subject.</span></b></p>
<p class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></p>
<p class="MsoNormal"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US">References:</span></b></p>
<p style="margin-left:36pt"><b><span style="font-size:9pt;font-family:Arial" lang="EN-US">A.<span> </span></span></b><b><u><span style="font-size:9pt;font-family:Arial" lang="EN-US">Integrative
Medicine</span></u></b></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Integrative
Medicine: </span><a href="http://www.wikiwand.com/en/Integrative_medicine" style="font-family:Arial;font-size:9pt" target="_blank">https://en.wikipedia.org/wiki/Integrative_medicine</a></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">What Is
Integrative Medicine?:</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="DE"><a href="http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine" target="_blank"><span lang="EN-US"></span></a><a href="http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine" target="_blank">http://www.webmd.com/a-to-z-guides/features/alternative-medicine-integrative-medicine</a></span><span style="font-size:9pt;font-family:Arial" lang="EN-US"></span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Integrative
Medicine Research:</span></p>
<p class="MsoNormal" style="margin-left:36pt"><cite><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US"><a href="http://www.journals.elsevier.com/integrative-medicine-research/" target="_blank">http://www.journals.elsevier.com/integrative-medicine-research/</a></span></cite></p>
<p class="MsoNormal" style="margin-left:36pt"><cite><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US"> </span></cite></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Advances
in Integrative Medicine</span><span style="font-size:9pt;font-family:Arial" lang="EN-US"></span></p>
<p class="MsoNormal" style="margin-left:36pt"><cite><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US"><a href="http://www.journals.elsevier.com/advances-in-integrative-medicine" target="_blank">http://www.journals.elsevier.com/advances-in-integrative-medicine</a></span></cite></p>
<p class="MsoNormal" style="margin-left:36pt"><cite><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US"> </span></cite></p>
<p style="margin-left:36pt"><cite><b><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US">B.<span>
</span></span></b></cite><cite><b><u><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US">Integral Biomathics</span></u></b></cite></p>
<p style="margin-left:36pt"><cite><span style="font-size:9pt;font-family:Arial;font-style:normal" lang="EN-US">Integral Biomathics:</span></cite></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://www.wikiwand.com/en/Integral_Biomathics" target="_blank"></a><a href="https://en.wikipedia.org/wiki/Integral_Biomathics" target="_blank">https://en.wikipedia.org/wiki/Integral_Biomathics</a></span><b><i><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></i></b></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Integral
Biomathics: A Post-Newtonian View into the
Logos of Bios </span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="https://arxiv.org/ftp/cs/papers/0703/0703002.pdf" target="_blank"></a><a href="https://arxiv.org/ftp/cs/papers/0703/0703002.pdf" target="_blank">https://arxiv.org/ftp/cs/papers/0703/0703002.pdf</a></span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">On Some
Recent Insights in Integral Biomathics:</span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf" target="_blank"></a><a href="https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf" target="_blank">https://arxiv.org/ftp/arxiv/papers/1306/1306.2843.pdf</a>.</span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Integral
Biomathics Reloaded: 2015 (free access until
July 19<sup>th</sup> 2016):</span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://www.sciencedirect.com/science/article/pii/S0079610715001509" target="_blank"></a><a href="http://www.sciencedirect.com/science/article/pii/S0079610715001509" target="_blank">http://www.sciencedirect.com/science/article/pii/S0079610715001509</a></span></p>
<p class="MsoNormal" style="text-indent:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><b><span style="font-size:9pt;font-family:Arial" lang="EN-US">C.<span> </span></span></b><b><u><span style="font-size:9pt;font-family:Arial" lang="EN-US">Self-organized
criticality</span></u></b><u><span style="font-size:9pt;font-family:Arial" lang="EN-US">:</span></u></p>
<p class="MsoNormal"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Self-organized
criticality:</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://www.wikiwand.com/en/Self-organized_criticality" target="_blank"></a><a href="https://en.wikipedia.org/wiki/Self-organized_criticality" target="_blank">https://en.wikipedia.org/wiki/Self-organized_criticality</a></span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Self-organized
criticality (SOC):</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://www.johnboccio.com/courses/SOC26/15-SOC.pdf" target="_blank"></a><a href="http://www.johnboccio.com/courses/SOC26/15-SOC.pdf" target="_blank">http://www.johnboccio.com/courses/SOC26/15-SOC.pdf</a></span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Self-organized
criticality:</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf" target="_blank"></a><a href="http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf" target="_blank">http://web.mit.edu/8.334/www/grades/projects/projects12/V.%20A.%20Golyk.pdf</a></span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Self-organized
criticality – what it
is and what it isn’t</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf" target="_blank"></a><a href="http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf" target="_blank">http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.96.8017&rep=rep1&type=pdf</a>.
</span></p>
<p class="MsoNormal"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><b><span style="font-size:9pt;font-family:Arial" lang="EN-US">D.<span> </span></span></b><b><u><span style="font-size:9pt;font-family:Arial" lang="EN-US">Phenomenology
in Medicine</span></u></b></p>
<p class="MsoNormal"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial;color:rgb(3,37,17)" lang="EN-US">The meaning of illness:
a phenomenological approach to the physician/patient
relationship: <a href="https://baylor-ir.tdl.org/baylor-ir/handle/2104/8286" target="_blank">https://baylor-ir.tdl.org/baylor-ir/handle/2104/8286</a>
; </span><span style="font-size:9pt;font-family:Arial;color:rgb(38,38,38)" lang="EN-US"><a href="http://hdl.handle.net/2104/8286" target="_blank">http://hdl.handle.net/2104/8286</a>.
</span><span style="font-size:9pt;font-family:Arial;color:rgb(3,37,17)" lang="EN-US"></span></p>
<p class="MsoNormal"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Body
Matters: A Phenomenology of
Sickness, Disease, and Illness:</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="http://philpapers.org/rec/AHOBMA" target="_blank"></a><a href="http://philpapers.org/rec/AHOBMA" target="_blank">http://philpapers.org/rec/AHOBMA</a>.
</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Suffering
Transfigured: Phenomenological Personalism In the
Doctor-Patient Relationship: <a href="http://elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1658&context=ymtdl" target="_blank">http://elischolar.library.yale.edu/cgi/viewcontent.cgi?article=1658&context=ymtdl</a>.</span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">The
challenge of
neuroscience: Psychiatry and phenomenology today: </span><span style="font-size:9pt;font-family:Arial" lang="EN-US"><a href="https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf" target="_blank"></a><a href="https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf" target="_blank">https://www.klinikum.uni-heidelberg.de/fileadmin/zpm/psychatrie/fuchs/Challenge_of_Neuroscience.pdf</a>.</span><span style="font-size:9pt;font-family:Arial" lang="EN-US">
</span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US"> </span></p>
<p class="MsoNormal" style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">Rediscovering
Psychopathology: The Epistemology and Phenomenology </span><span style="font-family:Arial;font-size:9pt">of the Psychiatric
Object:
</span><a href="http://cfs.ku.dk/staff/zahavi-publications/Rediscovering_Psychopathology.pdf" style="font-family:Arial;font-size:9pt" target="_blank">http://cfs.ku.dk/staff/zahavi-publications/Rediscovering_Psychopathology.pdf</a><span style="font-family:Arial;font-size:9pt">.</span></p>
<p style="margin-left:36pt"><span style="font-size:9pt;font-family:Arial" lang="EN-US">PHENOMENOLOGY
IN PSYCHIATRY:
<a href="http://www.wpanet.org/uploads/Sections/Philosopy_and_Humanities/Phenomenology-in-Psychiatry.pdf" target="_blank">http://www.wpanet.org/uploads/Sections/Philosopy_and_Humanities/Phenomenology-in-Psychiatry.pdf</a>.
</span></p>
<div>
<div>
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<div dir="ltr">
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<div dir="ltr">
<div dir="ltr">
<div dir="ltr"><b><span style="font-size:10pt;font-family:Arial" lang="EN-US"> </span></b></div>
<div><font face="Arial"><b>Plamen</b></font></div>
<div dir="ltr">
<div>____________________________________________________________</div>
<div><span style="font-family:georgia,serif"><a href="http://www.sciencedirect.com/science/journal/00796107/119/3" target="_blank">2015 JPBMB Special
Issue on Integral Biomathics: Life
Sciences, Mathematics and
Phenomenological Philosophy</a> </span></div>
<div><span style="font-family:georgia,serif">(note:
free access to all articles until July
19th, 2016)</span></div>
<div><span style="font-family:georgia,serif"><br>
</span></div>
<div><font face="georgia, serif"><a href="http://www.sciencedirect.com/science/journal/00796107/113/1" target="_blank">2013 JPBMB Special
Issue on Integral Biomathics: Can
Biology Create a Profoundly New
Mathematics and Computation?</a></font></div>
<div><br>
</div>
<div><font face="georgia, serif"><a href="http://www.springer.com/engineering/computational+intelligence+and+complexity/book/978-3-642-28110-5" target="_blank">2012 Integral
Biomathics: Tracing the Road to
Reality</a></font></div>
<div><br>
</div>
<div><a href="http://www.inbiosa.eu" style="font-family:georgia,serif" target="_blank">2011 INtegral
BIOmathics Support Action (INBIOSA)</a> </div>
<div>
<div>____________________________________________________________</div>
</div>
<div><br>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</div>
</blockquote>
<br>
<p><br>
</p>
</div></div><span class=""><font color="#888888"><pre cols="72">--
-------------------------------------------------
Pedro C. Marijuán
Grupo de Bioinformación / Bioinformation Group
Instituto Aragonés de Ciencias de la Salud
Centro de Investigación Biomédica de Aragón (CIBA)
Avda. San Juan Bosco, 13, planta X
50009 Zaragoza, Spain
Tfno. <a href="tel:%2B34%20976%2071%203526" value="+34976713526" target="_blank">+34 976 71 3526</a> (& 6818)
<a href="mailto:pcmarijuan.iacs@aragon.es" target="_blank">pcmarijuan.iacs@aragon.es</a>
<a href="http://sites.google.com/site/pedrocmarijuan/" target="_blank">http://sites.google.com/site/pedrocmarijuan/</a>
-------------------------------------------------
</pre>
</font></span></div>
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