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White Paper                  13 March 2013



Innoception Technologies LLC is pioneering an Integrative Health platform for untethered
measurement of health parameters for an online, cloud-based format. This platform combines
off-the-shelf and proprietary technologies from a recently successful crowdsourcing effort to
produce a reliable, consistent process that quantizes wellness. This collaboration brings the most
progressive available technologies together on a platform that will allow the customer to track
his/her health in a dynamic and accurate online way.
It has been surmised for some time that there is an optimum range of physiological functioning
that will allow health providers unprecedented accuracy in assigning customers to wellness
profiles across demographic and diagnostic groups. Our approach to capturing this
neurophysiological state takes into account the diversity of the human species, reflecting the
genomic adaptability that explains our success on this planet. Revealing physiological baseline
information in a dynamic context goes beyond the understanding of traditional medicine in
regards to disease management to a predictive one that emphasizes the importance of returning
the individual to his/her optimum physiological baseline. Operating within their unique
parameters will make possible their most efficient use of medical interventions and allow quick
rehabilitation and recovery from health challenges of all kinds. This approach will also reveal
new information about global wellness issues like immune system functioning and recovery,
since the immune system’s optimum functioning is the true key to lifelong wellness. This paper
presents an overview of the collaborative roles that will allow this approach to Integrative Health
and wellness to succeed and give a concise and integrative view of the true promise of
personalized health.
This paper discusses the format for this ongoing enquiry along with the market forces which
affect the adoption of a new approach to health that emphasizes wellness. A unique collaboration
among several existing businesses and their proprietary technologies will allow this effort to
proceed. Also, the location at the University of Utah will give access to critical resources for
genomic enquiry and data management that exist nowhere else. Innoception Technologies LLC is
a Medical Technology startup licensed at the University of Utah Technology Commercialization
Office. We are unique in having a broad support base across five major departments at the U/U.
We have two specific patents licensed to us that offer us impressive market advantages. One is a
process patent for concurrent measurement of biosignals during a therapeutic or medical
intervention. Another is a unparalleled approach to ‘big data,’ “NDV” or n-dimensional
visualization developed by the head of our science advisory board and former head of Computer
Science at the U/U, Robert Johnson PhD. Analysis of biosignals with their orthogonal fields adds
to the specificity and sensitivity of accurate diagnostic formulations. Individuals within our team
have been measuring patterns made by the brain/body’s physiological subsystems since 2005.
We have rediscovered the nonlinear nature of biological systems, where system output is not a
straight line function of its input. Nonlinear systems are both stable and flexible as they go about
task performance. We have chosen three physiological signals that fluctuate orthogonally to each
other, allowing us to define a “corridor of normal”, age and sex specific, for each biosignal,
where individual clinical conditions fall outside this corridor in characteristic ways.
On a small scale, many studies have shown the utility of applying multivariate analysis and data
mining techniques to medical data. Innoception’s approach will be unique for examining the
collective effect of many parameters for relevance to health disorders. Multiparameter analysis
(MPA) techniques include vector fusion, Shannon information analyses and other topological
data mining approaches. These are expected to indicate how specific groups of bio-signal
parameters collectively enhance or diminish correlation patterns with specific neurophysiological
states associated with anxiety disorders, for example. Development of effective MPA methods,
using archived data when possible, will be the focus during the first year. Standard statistical
approaches in medical research are generally too limited to appreciate the physiological diversity
that determines lifelong wellness. The challenges of capturing optimum human functioning are
also the challenges of ‘big data’ and in the future, HIPAA-related concerns for data capture and
maintenance will not only focus on patient protection but also the ability to maintain the Value of
Information (VOI). As a part of healthcare reform, many health stakeholders are grappling at
present with the portability of information across HIEs (Health Information Exchanges) where
most traditional health entities are for the first time addressing core empirical issues in terms of
how meaningful health data is captured and maintained in the context of personalized healthcare
and the integration of dissimilar data sources. The proposed collaboration will result in a ‘best
practices’ model since biophysiological data will be analyzed across a spectrum of integrative
health interventions which evidence the greatest therapeutic benefit in these conditions. Then
healthy information will lead to a greater variety of choices for the healthcare consumer and
allow a collaborative approach to health. Biopsychosocial phenomenon and social factors
dynamically interact and affect the individual’s ability to adapt. The most promising therapies for
traumatically induced biophysiological conditions are often integrative and holistic approaches to
symptom management.
   I. Traumatic experience, disability and Health Events:

The heart receives neural stimulation from both the sympathetic and parasympathetic ANS
components.      Blood pressure regulation is one of the most important ANS functions.
Baroreceptor cells in the heart and blood vessels sense pressure and send afferent signals to the
brain where components of the ANS that control heart rate and vascular tonus via sympathetic,
and to a lesser extent parasympathetic, activity. This is a dedicated feedback control system to
maintain blood pressure within proper limits by adjusting heart rate and cardiac output in
response to environmental and emotional influences. Thus heart rate is recognized as a basic
measure of ANS function.       Other factors affecting cardiac regulation include respiration,
thermoregulation, and humoral regulation, whose ANS influences also reflect neurophysiological
status is subtle ways.

The cardiovascular bio-signal parameters briefly described below reflect various aspects of ANS
activity; they will be studied using multiparameter analysis for relevancy as potential individual
or clustered markers for anxiety disorders.

Blood Pressure

Heart Rate (HR) High resting heart rate is also associated with increased risks of adverse
outcomes for coronary artery disease (CAD).

Heart Rate Variability (HRV) is an important parameter for reflecting ANS status.
Physiologically, a significant increase in HF/LF power, followed by a sharp decrease is cited as a
predictor of paroxysmal atrial fibrillation (PAF), and low HRV reflects poor cardiac health.
Complicating issues include HRV reflection of both sympathetic and parasympathetic activity,
and significant HRV differences are commonly found between individuals.

P-wave dispersion and variability have been the focus of several recent research studies. The Q-
T interval A technique using root-mean square values across multiple ECG leads has been used at
the University of Utah to obtain reliable Q-T intervals for research projects. QT dispersion may
be associated with increased risks of arrhythmic events and syncope, and it may predict sudden
cardiac death in variety of disease states such as acute myocardial infarction and hypertrophic
cardiomyopathy.

Respiratory Sinus Arrhythmia (RSA) is related to the HF peak in the HRV spectrum and it
primarily indicates parasympathetic ANS activation

Baroreflex sensitivity (BRS) associates reduced parasympathetic function with PTSD in males,
but a recent study found contrary gender effects in BRS among smokers.

Vagal tone is a positive indicator of stress and is considered important parameters for
characterizing anxiety disorders.

The characteristics of these bio-signals will be studied and classified quantitatively as potential
contributors for developing multiparameter bio-signal marker patterns for neurophysiological
conditions and states such as anxiety disorders.

1.- ECG
2.- Diastolic Blood Pressure (DBP)
3.- Systolic Blood Pressure (SBP)
4.- Glucose Test (GT)
5 .- Average glucose for the past 8 weeks test (H1A1c Test)
6.- Type of medication used.
7.- High Density Lipoprotein (HDL)
8.- Low Density Lipoprotein (LDL)
9.- Weight (WT)
10,- Fast Plasma Glucose test
11.- Body mass Index (BMI)
We will be seeking to additionally develop new areas where the analysis methods and data
mining approaches we possess offer great promise. For example, In 2000, according to the World
Health organization (WHO), at least 171 million people or 2.8% of the population suffered from
diabetes. The number is increasing rapidly, and by 2030, the number will double. Type 2 diabetes
is more common in the Western world, where urbanization and lifestyle changes have increased
the prevalence of the illness, and an environmental (dietary) affect is implied. Type 2 affects up
to 95% of the US diabetes population. 18.6% of those above 60 have diabetes, from the National
Health and Nutrition Examination Survey. In particular, the system we propose specifically
predicts the diabetes variables of a patient for the next scheduled doctor’s visit. Alarming values
in these predictions can trigger automatic warnings to the medical professional allowing for
scheduling more frequent visits, which allows the medical professional to timely intervene. To
predict the future diabetes variables from past data, we propose to use artificial intelligence and
machine learning techniques. Our algorithms will be trained on the existing rich set of patient
data in the Utah diabetes database. Various AI and ML techniques are candidates to be adapted to
successfully achieve this goal. One approach would be to view the patient as a dynamical
system, whose dynamics equations (governing the evolution of its state over time) are unknown.
Various AI and ML techniques exist to learn these dynamics equations from past data. Given
such a dynamics model, it can readily be used to predict the patient’s state into the future, and it
is able to provide a measure of (un)certainty about its prediction. Another class of techniques
builds on Artificial neural networks (ANN), which is a powerful empirical pattern-recognition
and mapping tool for different data, including approximation of complex nonlinear relationships,
as well as different outcomes that characterize individualized epidemiological trajectories. In
personalized healthcare, these trajectories are revealed as epigenetic influences accompanied by
discrete medical indicators. Instead of imposing an a priori model on the data, ANN learns input
and output relationships directly from the data. The flexibility of the ANN models has led to
successful application in population pharmacokinetic and pharmacodynamic data analysis.
Standard medical information and local clinical studies will be related to one or more
conventional psychiatric scale metrics such as the Hamilton Anxiety Scale, Hamilton Depression
Scale, Positive and Negative Syndrome Scale, Clinician-administered PTSD Scale, Mississippi
Scale for Combat-Related PTSD, and Watson's criteria for PTSD in the veteran arms of the
studies. This provides well documented classification references for each bio-signal record.
Local clinical studies are planned for the second year to verify MPA results. Laboratory serum
assays will be collected to determine the levels of stress markers such as cytokines and
chemokines to further verify the results through multiparameter analysis techniques. Lastly, since
the ECG inherently reflects many aspects of the heart’s physical status, it is possible that in the
process of mining neurological information from ECG parameters, Innoception may also
uncover new marker patterns for certain cardiovascular conditions. This possibility is considered
a secondary facet of the proposed research project, and relevant discoveries in the cardiovascular
areas will be documented for further investigation. It should be observed that A-Fib and other
chronic heart conditions may have a higher incidence in veteran populations than in the general
population. Innoception will develop and employ multiparameter analysis techniques in a
structured investigation of complex bio-signal parametric relationships associated with anxiety
disorders in the ECG bio-signal. As progress is made in discovering collective ECG parameter
correlations to anxiety traits, additional bio-signal parameters from other bio-signals, such as
blood pressure, and skin conductance will be included in the study to develop a multi-modal
approach for objective neurological state analysis.
    II. Collaborators
Drs Ed Fila and Regina Drueding (co-founders) have been pioneers and successful entrepreneurs in CVD
prevention and CIMT development. They, in prior entities, developed the CIMT software that received
FDA approval, sold to an ultrasound manufacturer, and established several CIMT outsourcing companies
that today are the primary industry players. Dr. Fila has also been intimately involved in researching
cancer prevention (including researching facilities or practitioners getting exceptional results), treating
depression, getting metals out of the body, reducing effects of radiation, etc. (all major drivers of CVD),
A seasoned corporate executive, Fortune 500 consultant and entrepreneur, Bruce Collett will lead the
effort to establish cardiovascular measurement with this technology. Two other founders contribute
engineering, QC, project management, IT systems, marketing and business skills.
Tomasz Petelenz PhD and Robert Tuckett PhD will guide the bioengineering aspects of the project, both
with extensive experience in the assessment and measurement of relevant physiological parameters that
relate to health and wellness.
Proprietary technologies that will be utilized include biochemical analysis of the breath, developed by
Royce Johnson PhD, and the use of blood markers to quantize the neurological level of
functioning/injury developed by Banyan Pharma. We feature the combination of these new technologies
that we consider critical to the capture of a meaningful and accurate dynamic measurement of
physiological baseline and will actively collaborate with them in utilizing these proprietary technologies
on the Innoception platform.
Breath analysis for health diagnosis and management: The principle long-term target for EZKnowz™ is
for health diagnosis and health management, through breath or odor analysis. We all know that the
“elephant in the room” is the extremely high cost of healthcare and that current proposed solutions are
not adequate. In search of fresh approaches, it worth noting that the computer technology industry is
one of the few industries where the cost becomes lower year after year, driven by Moore’s Law, where
computer power doubles every 18 months. Creative coupling of this digital power offers a chance to rein
in the spiraling cost of healthcare. The question is: What is the optimal way of implementation of
computing power and internet communication in the healthcare industry?
One great possibility of healthcare cost reduction is to find a solution to “the fact that much time and
money is spent on patients visiting their doctors or a clinic and too little attention is afforded to
preventive care”. Improvements in preventive diagnostics will help reduce hospital admission costs and
allow patients to be cared for at home, for longer. The biggest issue is keeping patients out of hospitals.
Simple diagnostic devices are needed that operate at the personal level and that can universally monitor
the health status of individuals in a home environment in real time. These diagnostic devices should be
able to digitize the collected information and use the internet to transfer data and communicate with the
doctor’s offices. Powerful consumer gadgets already exist that are simple to use and consistent with the
existing PCs infrastructure, whether this is smart phone, IPad, a notebook, etc. Our vision is to emulate
the IT/PC revolution by empowering the individuals with digital, personal, real time monitoring devices
for the purpose of preventive care and facilitating early diagnostics. why we cannot communicate with
doctors without face to face meetings, and there is no reason that preventive care should not have
excellent remote medical coverage. We and many others believe that there is a huge business
opportunity here!
For example, one study has identified as many as 3,481 components in human breath. Already
correlations between increases in specific components (markers) with physiological sources and
conditions have been identified (lung cancer, influenza, tuberculosis, etc.). Advantages are:
 Non-invasive (painless),

 Sample is easy acquire,

 Information rich,

 Digital information available immediately,

 Low-cost and easy to administer.


Patented claims to protect these concepts and the first issued claims are published in “Analysis of Gases”
(Issued European Patent EP 1 976 431 B1).
Use of biomarkers in neurological functioning/injury. Although there are a number of
biochemical markers that have been investigated in TBI, our discussion will include the most
current and widely studied ones. The most extensively studied among these are glial protein S-
100 beta(β) 45-55, neuron-specific enolase (NSE)56-63, and myelin basic protein (MBP)41, 59,
64-66 Although some of these published studies suggest that these biomarkers correlate with
degree of injury; conflicting results exist (3-11). S100β is the major low affinity calcium binding
protein in astrocytes (3) and it is considered a marker of astrocyte injury or death. It can also be
found in non-neural cells such as adipocytes, chondrocytes, and melanoma cells (12). Elevated
serum levels have been associated with increased incidence of post concussive syndrome and
impaired cognition (13,14). Other studies have reported that serum levels of S-100β are
associated with MRI abnormalities and with neuropsychological examination disturbances after
mild TBI (15,16). A number of studies have found significant correlations between elevated
serum levels of S-100β and CT abnormalities (17-19). It has been suggested that adding the
measurement of S-100B concentration to clinical decision tools for mild TBI patients could
potentially reduce the number of CT scans by 30%.84 Other investigators have failed to detect
associations between S-100β with CT abnormalities (3,20-22). The vast majority of these clinical
studies have employed ELISA to measure levels of S100B. Although S-100β continues to be
actively investigated and remains promising as an adjunctive marker, its utility as a biochemical
diagnostic remains controversial. Some studies have observed high serum S-100β levels in
trauma patients without head injuries suggesting that it lacks CNS specificity and is released
from peripheral tissues (23-25).
Neuron specific enolase is one of the five isozymes of the gycolytic enzyme enolase found in
central and peripheral neurons and it has been shown be elevated following cell injury (26). It
has a molecular weight of 78 kDa and a biological half-life of 48 hours (27). This protein is
passively released into the extracellular space only under pathological conditions during cell
destruction.
Most studies employed an enzyme immunoassay for NSE detection. Many of these studies either
contained inadequate control groups or concluded that serum NSE had limited utility as a marker
of neuronal damage. Early levels of NSE and MBP concentrations have been correlated with
outcome in children, particularly those under 4 years of age(1,2,28,29). A limitation of NSE is
the occurrence of false positive results in the setting of hemolysis (30).
A supposedly cleaved form of tau, c-tau, has also been investigated as a potential biomarker of
CNS injury. Tau is preferentially localized in the axon and tau lesions are apparently related to
axonal disruption (31,32). CSF levels of c-tau were significantly elevated in TBI patients
compared to control patients and these levels correlated with clinical outcome (33,34). Though
levels of c-tau were also elevated in plasma from patients with severe TBI, there was no
correlation between plasma levels and clinical outcome. A major limitation of all of these
biomarkers is the lack of specificity for defining neuropathological cascades.
Using the same proteomic Western blot technique, levels of spectrin breakdown products
(SBDP’s) have been reported in CSF from adults with severe TBI and they have shown a
significant relationship with severity of injury and clinical outcome (35-40). Following a TBI the
axonally enriched cytoskeletal protein -II-spectrin is proteolyzed by calpain and caspase-3 to
signature breakdown products (SBDPs). Calpain and caspase-3 mediated SBDP levels in CSF
have shown to be significantly increased in TBI patients at several time points after injury,
compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145
(markers of necrosis) differs from that of caspase-3 mediated SBDP120 (marker of apoptosis). A
promising candidate biomarker for TBI currently under investigation is Ubiquitin Cterminal
Hydrolase-L1 (UCH-L1). UCH-L1 was previously used as a histological marker for neurons due
to its high abundance and specific expression in neurons (41). This protein is involved in the
addition and removal of ubiquitin from proteins that are destined for metabolism (42). It has an
important role in the removal of excessive, oxidized or misfolded proteins during both normal
and pathological conditions in neurons (43). In initial studies, UCH-L1 was identified as a
protein with a two-fold increase in abundance in the injured cortex 48 hours after controlled
cortical impact in a rat model of TBI (44). Subsequently, a
UCH-L1 sandwich enzyme-linked immunosorbent assay quantitatively showed that CSF and
serum UCH-L1 levels in rats were significantly elevated as early as 2 hours following both
traumatic and ischemic injury (45). Clinical studies in humans with severe TBI confirmed, using
ELISA analysis, that the UCH-L1 protein was significantly elevated in human CSF44 (46), and
was detectable very early after injury and remained significantly elevated for 168 hours post-
injury. Further studies in severe TBI patients have revealed a very good correlation between CSF
and serum levels. Most recently, UCH-L1 was detected in the serum of mild and moderate TBI
(MMTBI) patients within an hour of injury. Serum levels of UCH-L1 discriminated MMTBI
patients from uninjured and non-head injured trauma controls and were also able to distinguish
mild TBI (concussion patients) from these controls. Most notable was that levels were
significantly higher in those with intracranial lesions on CT than those without lesions. Glial
Fibrillary Acidic Protein (GFAP) is a monomeric intermediate protein found in astroglial
skeleton that was first isolated by Eng et al. in 1971. GFAP is found in white and gray brain
matter and is strongly upregulated during astrogliosis. Current evidence indicates that serum
GFAP might be a useful marker for various types of brain damage from neurodegenerative
disorders (47,48) and stroke to severe traumatic brain injury (49-53).
Clinical researchers have developed methodological standards for developing clinical decision
tools in order to ensure the validity of study results (54,55). As TBI biomarker research
transitions from the bench to the bedside there are a number of important methodological issues
that researchers will have to consider as they design their clinical protocols. Since TBI
biomarkers are being designed for clinical management, the outcome or diagnosis being
examined will need to be clearly defined and clinically important. In order to ensure external
validity and the generalizability of the results, study patients will have to be selected without bias
and represent a wide spectrum of clinical and demographic characteristics. When interpreting the
data, clinical variables that potentially affect outcome will require careful consideration in the
analysis. Biochemical markers could help with clinical decision making by elucidating injury
severity, injury mechanism(s), and monitoring progression of injury. Temporal profiles of
changes in biomarkers could guide timing of diagnosis and treatment. Biomarkers could have a
role in management decisions regarding patients at high risk of repeated injury. Accurate
identification of these patients could facilitate development of guidelines for return to duty, work
or sports activities and also provide opportunities for counseling of patients suffering from these
deficits. Repeated mild TBI occurring within a short period (i.e. hours, days, or weeks) can be
catastrophic or fatal, a phenomenon termed ‘second impact syndrome.’
Acute CT or MRI abnormalities are not usually found after these injuries, but levels of some
neurotransmitters remain elevated, and a hypermetabolic state may persist in the brain for several
days after the initial injury.
Biomarkers could serve as prognostic indicators by providing information for patients and their
families about the expected course of recovery. It opens the door to the initiation of early
therapies. Identifying at-risk patients with less apparent TBI or differentiating injury pathology in
those with more severe intracranial processes would be tremendously valuable in the
management of these patients. For example, in a patient with a normal CT scan or MRI, a
biomarker that could predict worsening neurological status or long-term disability would have
great clinical utility.
There have been a large number of clinical trials studying potential therapies for traumatic brain
injury (TBI) that have resulted in negative findings. Biomarkers measurable in blood would have
important applications in clinical research of these injuries. Biomarkers could provide clinical
trial outcome measures that are cost-effective and more readily available than conventional
neurological assessments, thereby significantly reducing the risks and costs of human clinical
trials. Biomarkers that represent highly sensitive and specific indicators of disease pathways
have been used as substitutes for outcomes in clinical trials when evidence indicates that they
predict clinical risk or benefit.
Lack of quickly accessible pathophysiologic information during the post-injury course has made
pharmacologic intervention problematic. Biomarkers could provide more timely information on
disease progression and the effects of interventions such as drugs and surgery. Biomarker
measurements could potentially relate the effects of interventions on molecular and cellular
pathways to clinical responses. In doing so, biomarkers would provide an avenue for researchers
and clinicians to gain a mechanistic understanding of the differences in clinical response that
may be influenced by uncontrolled variables.
Intoxicated, unconscious, sedated, or polytraumatized patients suspected of having a TBI pose a
particular challenge to emergency and trauma physicians. Biomarkers could expedite the
evaluation of such patients by providing information on the degree of brain injury prior to
neuroimaging. Biomarkers in this setting could also help determine the need for early
neurosurgical consultation or transfer to facilities with neurosurgical capabilities. There are
potential military applications as well. Serum biomarkers could help diagnose and/or triage brain
injured military servicemen and women. TBI is a leading cause of combat casualty with an
estimated 15-20% of all injuries sustained in 20th century conflicts being to the head (57-58).
America's armed forces are sustaining attacks by rocket-propelled grenades, improvised
explosive devices, and land mines almost daily in the recent conflicts in Iraq and
Afghanistan.145 It has been suggested that over 50% of injuries sustained in combat are the
result of such explosive munitions including bombs, grenades, land mines, missiles, and
mortar/artillery shells. Neuroimaging techniques to diagnose brain injury acutely and other
monitoring tools that assess secondary insults are not immediately available in combat zones and
such casualties have to be evacuated. Triage and management of brain injured soldiers could be
significantly improved if first responders had a quick and simple means of objectively assessing
severity of brain injury and of
monitoring secondary insults.
There is a unique opportunity to use the insight offered by biochemical markers to shed light on
the complexities of the injury process. Accordingly, certain markers could be used as indicators
of damage to a particular cell type or cellular process or may be indicative of a particular type of
injury. Neuroanatomically, that could include evidence of, say, primary axonal damage versus
glial damage. With such heterogeneity the solution may not lie with a single biomarker but more
with a complementary panel of markers that may prove useful in distinguishing different
pathoanatomic processes of injury.


    III. Development of Healthbooks™
In the business model using software as a service (SaaS), users are provided access to application
software and databases. The cloud providers manage the infrastructure and platforms on which the
applications run. SaaS is sometimes referred to as “on-demand software” and is usually priced on a pay-
per-use basis. SaaS providers generally price applications using a subscription fee.
    •   Proponents claim that the SaaS allows a business the potential to reduce IT operational
        costs by outsourcing hardware and software maintenance and support to the cloud
        provider. This enables the business to reallocate IT operations costs away from
        hardware/software spending and personnel expenses, towards meeting other IT goals. In
        addition, with applications hosted centrally, updates can be released without the need for
        users to install new software. One drawback of SaaS is that the users' data are stored on
        the cloud provider’s server. As a result, there could be unauthorized access to the data.
        End users access cloud-based applications through a web browser or a light-weight
        desktop or
mobile app while the business software and user's data are stored on servers at a remote location.
Proponents claim that cloud computing allows enterprises to get their applications up and running
faster, with improved manageability and less maintenance, and enables IT to more rapidly adjust
resources to meet fluctuating and unpredictable business demand.
In the most basic cloud-service model, providers of IaaS offer computers - physical or (more often)
virtual machines - and other resources. (A hypervisor, such as Xen or KVM, runs the virtual machines as
guests. Pools of hypervisors within the cloud operational support-system can support large numbers of
virtual machines and the ability to scale services up and down according to customers' varying
requirements.) IaaS clouds often offer additional resources such as images in a virtual-machine image-
library, raw (block) and file-based storage, firewalls, load balancers, IP addresses, virtual local area
networks (VLANs), and software bundles. IaaS-cloud providers supply these resources on-demand from
their large pools installed in data centers. For wide-area connectivity, customers can use either the
Internet or carrier clouds (dedicated virtual private networks).
Cloud computing relies on sharing of resources to achieve coherence and economies of scale similar to a
utility (like the electricity grid) over a network. At the foundation of cloud computing is the broader
concept of converged infrastructure and shared services.
The underlying concept of cloud computing dates back to the 1950s, when large-scale mainframe
became available in academia and corporations, accessible via thin clients / terminal computers. To make
more efficient use of costly mainframes, a practice evolved that allowed multiple users to share both the
physical access to the computer from multiple terminals as well as to share the CPU time. This
eliminated periods of inactivity on the mainframe and allowed for a greater return on the investment.
The practice of sharing CPU time on a mainframe became known in the industry as time-sharing.
In the 1990s, telecommunications companies, who previously offered primarily dedicated point-to-point
data circuits, began offering virtual private network (VPN) services with comparable quality of service
but at a much lower cost. By switching traffic to balance utilization as they saw fit, they were able to
utilize their overall network bandwidth more effectively. The cloud symbol was used to denote the
demarcation point between that which was the responsibility of the provider and that which was the
responsibility of the users. Cloud computing extends this boundary to cover servers as well as the
network infrastructure. As computers became more prevalent, scientists and technologists explored
ways to make large-scale computing power available to more users through time sharing, experimenting
with algorithms to provide the optimal use of the infrastructure, platform and applications with
prioritized access to the CPU and efficiency for the end users.


Gathering data is a fairly easy task, understanding it is the problem. Big data presents a
challenge in that the value of information (VOI) becomes a key consideration- allowing the
meaning of medical data to the patient will be considered a HIPAA violation in the furue. Today
we rely heavily on digital data streams to analyze everything from the timing microwave ovens
to listening to music from an iPhone. One characteristic of digital data is that is very mundane –
it is very much like Morse code. At least in Morse code there was a long sound and a short
sound. maybe even some rhythm Some very adept in Morse code could understand the various
clicks as a language. Digital data would not be very practical without a computer. - imagine
reading this document in Morse code! Fortunately, modern fast computers exist to eliminate that
boredom..
Let's look at our objective: Provide a improved quality of life through a few simple, unobtrusive
devices that provide a constant stream of digital data concerns our current health status. One,
unusual, benefit of constant health monitoring is now we will now what is right. If you are
flying North and you have a cross wind to the West it is obvious – to correct - one needs to fly a
little bit East. The key is a constant data stream that is routinely interpreted for all aspects of
health – those that are bad, those that are good and all those in between. Collected data is then
normalized for each individual that can be compared to the general populace instead of the other
way around. Once a data stream is collected it can then be easily transformed to be easily
understood much like this document had be transformed from Morse code. HIPAA compliance
requires that the architecture of the system be designed for failure- not just the interruption of the
data-architecture but the loss of connections that are essential to preserve the meaning of the
data.




Failure to decouple the links between the applications and the sources of data, especially when
they are likely to be so numerous, would be catastrophic. Applications must not be designed to
expect data, especially transient data, but the application and the device must be expected to
intercommunicate—but to execute completely independent of each other. A last example to
consider is the accelerating pace of business itself. Back-office systems have been designed and
built for years to run with extremely high performance and throughput. These back-office
systems have been measured by transactions per second, and response times to the submission of
an individual piece of work. As teams move to accessing and even running these solutions
outside the enterprise, they continue to expect the reliability and the speed of response seen
within the enter-prise domain. To try to achieve this will require substantial evaluation of how to
implement this connectivity to try to balance these requests. When it comes to responding to
requests, delays of even a second or more may lead to users to believe that there is be a problem,
and a negative perception can lead to rapid dissatisfaction with the solution.
The growth of cloud computing has created a change in this picture. Cloud is not a single thing, but
in fact can be used to describe the more-dynamic allocation and use of in-house IT resources, or
cloud can mean the use as needed of publically available IT resources on a usage-based model.
Or cloud could be any combination of these—and even other—deployment types. Business
leaders are likely to be considering which of their IT systems, and which of their applications,
are suitable for deployment in the cloud—whatever cloud might mean to them. Perhaps this
might be for cost-saving reasons, or it might be for more flexible deployment in response to a
growth in usage, or it might simply be the fastest way to get something done. Whatever the
reason, applications will need to become ever more agnostic about their runtime environment,
and the connections they have to the rest of the enterprise. They will need to be loosely
connected, but reliably and securely connected, enabling business teams to make decisions on
deployment completely independent of the application architecture itself.
Applications and the business IT infrastructure itself needs to be robust enough, and must
perform fast enough, to consume and take action on all the data and all the events, in a timely
manner. Other data can be held and processed to extract the remaining value. Indeed, the
applications and infrastructure must be both high-performing and “smart.” Applications and
infrastructure must not only be able to recognize the data that was previously important, but must
change to be able to identify and act upon some of the rest of the Big Data, creating the new
business opportunities that Big Data represents, even while Big Data creates new challenges to
the IT infrastructure—the systems, the applications and the connections between them.
One final way to move data between applications is to use a dedicated middleware layer for enterprise
messaging. This is a similar approach to the embedded JMS messaging mentioned above, but avoids the
limitations of being Java only, and of only connecting to other instances running in the same application
server environment. The enterprise messaging approach also avoids some of the limitations of HTTP,
since you are able to use more loosely coupled requests, including both time- independence and
transactional integrity. And although it is different from a file transfer solution, enterprise messaging can
be used to enhance, replace or update an existing or a new file transfer-based approach without
application disruption. As discussed above, many business leaders use applications coded in Java,
running in an application server. Part of the Java standard is JMS—providing a messaging service as a
part of the programming model. Using JMS is therefore a natural way for such applications to move data
into an application and out of an application, and many application servers include a JMS provider to
“listen” for JMS requests and execute them. However, this will only work if both the sending application
and the receiving application are running a common JMS provider. Although JMS is a standard API, the
wire format is not standard, so different JMS providers cannot exchange messages




    IV. Our corporate advantages for the researcher include:
•   Alignment of Integrative Health with disciplines that focus on human stress/resilience
       makes alignment with that community a high priority biosignal analysis for those
       involved in the development of these new technologies
   •   Submission of grants through TCO (Technology Commercialization Office) avoids high
       administrative charges for grants submitted through OSP (Office of Sponsored Projects)
       by various University Departments
   •   Innoception will aggressively approach funding sources that are not available to most
       Academic or Medical projects
   •   Innoception creates a protected place for those involved in development and fielding of
       measurement technologies to fully mature their intellectual property, whether device, or
       curriculum focused, provides an accelerated path to market
   •   Ongoing work in biosignal technology development has overlooked the complex adaptive
       system. We offer unique technological resources to enable the investigation of this
       potentially fruitful area of enquiry
   •   Principles associated with Innoception have an established track record of years of
       involvement in the Integrative and Academic community with stable networks in
       Business and Allied Technologies




   References
[1] Berger RP, Adelson PD, Pierce MC, Dulani T, Cassidy LD, Kochanek PM. Serum
neuron-specific enolase, S100B, and myelin basic protein concentrations after
inflicted and noninflicted traumatic brain injury in children. J Neurosurg. Jul
2005;103(1 Suppl):61-68.
[2] Berger RP, Beers SR, Richichi R, Wiesman D, Adelson PD. Serum biomarker
concentrations and outcome after pediatric traumatic brain injury. J Neurotrauma.
Dec 2007;24(12):1793-1801.
[3] Piazza O, Storti MP, Cotena S, et al. S100B is not a reliable prognostic index in
paediatric TBI. Pediatr Neurosurg. 2007;43(4):258-264.
[4] Martens P. Serum neuron-specific enolase as a prognostic marker for irreversible brain
damage in comatose cardiac arrest surviviors. Acad Emerg Med. 1996;3:126-131.
[5] Rainey T, Lesko M, Sacho R, Lecky F, Childs C. Predicting outcome after severe
traumatic brain injury using the serum S100B biomarker: results using a single
(24h) time-point. Resuscitation. Mar 2009;80(3):341-345.
[6] Bazarian JJ, Zemlan FP, Mookerjee S, Stigbrand T. Serum S-100B and cleaved-tau are
poor predictors of long-term outcome after mild traumatic brain injury. Brain Inj.
Jun 2006;20(7):759-765.
[7] Watt SE, Shores EA, Baguley IJ, Dorsch N, Fearnside MR. Protein S-100 and
neuropsychological functioning following severe traumatic brain injury. Brain Inj.
Sep 2006;20(10):1007-1017.
[8] Morochovic R, Racz O, Kitka M, et al. Serum S100B protein in early management of
patients after mild traumatic brain injury. Eur J Neurol. Oct 2009;16(10):1112-1117.
[9] Dirnagl U CI, and Moskowitz MA. Pathology of ischaemic stroke: an integrated view.
TINS. 1999;22(9):391-397.
[10] Laskowitz ea. Serum Markers of Cerebral Ischemia. Journal of Stroke and Cerebrovascular
Diseases. 1998;7(4 (July-August)):234-241.
[11] Roine ea. Neurological outcome after out-of-hospital cardiac arrest. Prediction by
cerebrospinal fluid enzyme analysis. Arch Neurol. 1989;46:753-756.
[12] Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history,
function, and expression. Brain Res Bull. 1995;37(4):417-429.
[13] Ingebrigtsen T, Romner B. Management of minor head injuries in hospitals in Norway.
Acta Neurol Scand. Jan 1997;95(1):51-55.
[14] Waterloo K, Ingebrigtsen T, Romner B. Neuropsychological function in patients with
increased serum levels of protein S-100 after minor head injury. Acta Neurochir
(Wien). 1997;139(1):26-31; discussion 31-22.
[15] Ingebrigtsen T, Romner B. Serial S-100 protein serum measurements related to early
magnetic resonance imaging after minor head injury. Case report. J Neurosurg. Nov
1996;85(5):945-948.
[16] Ingebrigtsen T, Waterloo K, Jacobsen EA, Langbakk B, Romner B. Traumatic brain
damage in minor head injury: relation of serum S-100 protein measurements to
magnetic resonance imaging and neurobehavioral outcome. Neurosurgery. Sep
1999;45(3):468-475; discussion 475-466.
[17] Ingebrigtsen T, Romner B, Marup-Jensen S, et al. The clinical value of serum S-100
protein measurements in minor head injury: a Scandinavian multicentre study.
Brain Inj. Dec 2000;14(12):1047-1055.
[18] Muller K, Townend W, Biasca N, et al. S100B serum level predicts computed
tomography findings after minor head injury. J Trauma. Jun 2007;62(6):1452-1456.
[19] Biberthaler P, Linsenmeier U, Pfeifer KJ, et al. Serum S-100B concentration provides
additional information fot the indication of computed tomography in patients after
minor head injury: a prospective multicenter study. Shock. May 2006;25(5):446-453.
[20] Phillips JP, Jones HM, Hitchcock R, Adama N, Thompson RJ. Radioimmunoassay of
serum creatine kinase BB as index of brain damage after head injury. Br Med J. Sep
20 1980;281(6243):777-779.
[21] Rothoerl RD, Woertgen C, Holzschuh M, Metz C, Brawanski A. S-100 serum levels after
minor and major head injury. J Trauma. Oct 1998;45(4):765-767.
[22] Bechtel K, Frasure S, Marshall C, Dziura J, Simpson C. Relationship of serum S100B
levels and intracranial injury in children with closed head trauma. Pediatrics. Oct
2009;124(4):e697-704.
[23] Rothoerl RD, Woertgen C. High serum S100B levels for trauma patients without head
injuries. Neurosurgery. Dec 2001;49(6):1490-1491; author reply 1492-1493.
[24] Romner B, Ingebrigtsen T. High serum S100B levels for trauma patients without head
injuries. Neurosurgery. Dec 2001;49(6):1490; author reply 1492-1493.
[25] Anderson RE, Hansson LO, Nilsson O, Dijlai-Merzoug R, Settergen G. High serum
S100B levels for trauma patients without head injuries. Neurosurgery.
2001;49(5):1272-1273.
[26] Skogseid IM, Nordby HK, Urdal P, Paus E, Lilleaas F. Increased serum creatine kinase
BB and neuron specific enolase following head injury indicates brain damage. Acta
Neurochir (Wien). 1992;115(3-4):106-111.
[27] Schmechel D, Marangos PJ, Brightman M. Neurone-specific enolase is a molecular
marker for peripheral and central neuroendocrine cells. Nature. Dec 21-28
1978;276(5690):834-836.
[28] Varma S, Janesko KL, Wisniewski SR, et al. F2-isoprostane and neuron-specific enolase
in cerebrospinal fluid after severe traumatic brain injury in infants and children. J
Neurotrauma. Aug 2003;20(8):781-786.
[29] Bandyopadhyay S, Hennes H, Gorelick MH, Wells RG, Walsh-Kelly CM. Serum
neuron-specific enolase as a predictor of short-term outcome in children with
closed traumatic brain injury. Acad Emerg Med. Aug 2005;12(8):732-738.
[30] Johnsson P, Blomquist S, Luhrs C, et al. Neuron-specific enolase increases in plasma
during and immediately after extracorporeal circulation. Ann Thorac Surg. Mar
2000;69(3):750-754.
[31] Kosik KS, Finch EA. MAP2 and tau segregate into dendritic and axonal domains after
the elaboration of morphologically distinct neurites: an immunocytochemical study
of cultured rat cerebrum. J Neurosci. Oct 1987;7(10):3142-3153.
[32] Higuchi M, Lee VM, Trojanowski JQ. Tau and axonopathy in neurodegenerative
disorders. Neuromolecular Med. 2002;2(2):131-150.
[33] Shaw GJ, Jauch EC, Zemlan FP. Serum cleaved tau protein levels and clinical outcome
in adult patients with closed head injury. Ann Emerg Med. Mar 2002;39(3):254-257.
[34] Zemlan FP, Jauch EC, Mulchahey JJ, et al. C-tau biomarker of neuronal damage in
severe brain injured patients: association with elevated intracranial pressure and
clinical outcome. Brain Res. Aug 23 2002;947(1):131-139.
[35] Cardali S, Maugeri R. Detection of alphaII-spectrin and breakdown products in
humans after severe traumatic brain injury. J Neurosurg Sci. Jun 2006;50(2):25-31.
[36] Papa L, D’Avella D, Aguennouz M, et al. Detection of Alpha-II Spectrin And
Breakdown Products In Humans After Severe Traumatic Brain Injury [abstract].
Acad Emerg Med. May 2004;11(5).
[37] Papa L, Lewis SB, Heaton S, et al. Predicting Early Outcome Using Alpha-II Spectrin
Breakdown Products In Human CSF After Severe Traumatic Brain Injury [abstract].
Acad Emerg Med. May 2006;13(5 (Suppl 1)).
[38] Papa L, Pineda J, Wang KKW, et al. Levels of Alpha-II Spectrin Breakdown Products in
Human CSF and Outcome After Severe Traumatic Brain Injury [abstract]. Acad
Emerg Med. May 2005;12(5 (Suppl 1)).
[39] Farkas O, Polgar B, Szekeres-Bartho J, Doczi T, Povlishock JT, Buki A. Spectrin
breakdown products in the cerebrospinal fluid in severe head injury--preliminary
observations. Acta Neurochir (Wien). Aug 2005;147(8):855-861.
[40] Mondello S, Robicsek SA, Gabrielli A, et al. alphaII-spectrin breakdown products
(SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J
Neurotrauma. Jul 2010;27(7):1203-1213.
[41] Jackson P, Thompson RJ. The demonstration of new human brain-specific proteins by
high-resolution two-dimensional polyacrylamide gel electrophoresis. J Neurol Sci.
Mar 1981;49(3):429-438.
[42] Tongaonkar P, Chen L, Lambertson D, Ko B, Madura K. Evidence for an interaction
between ubiquitin-conjugating enzymes and the 26S proteasome. Mol Cell Biol. Jul
2000;20(13):4691-4698.
[43] Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative
disorders. Drug News Perspect. Jul-Aug 2007;20(6):365-370.
[44] Kobeissy FH, Ottens AK, Zhang Z, et al. Novel differential neuroproteomics analysis of
traumatic brain injury in rats. Mol Cell Proteomics. Oct 2006;5(10):1887-1898.
[45] Liu MC, Akinyi L, Scharf D, et al. Ubiquitin C-terminal hydrolase-L1 as a biomarker
for ischemic and traumatic brain injury in rats. Eur J Neurosci. Feb 2010;31(4):722-
732.
[46] Siman R, Toraskar N, Dang A, et al. A panel of neuron-enriched proteins as markers
for traumatic brain injury in humans. J Neurotrauma. Nov 2009;26(11):1867-1877.
[47] Baydas G, Nedzvetskii VS, Tuzcu M, Yasar A, Kirichenko SV. Increase of glial fibrillary
acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of
vitamin E. Eur J Pharmacol. Feb 21 2003;462(1-3):67-71.
[48] Mouser PE, Head E, Ha KH, Rohn TT. Caspase-mediated cleavage of glial fibrillary
acidic protein within degenerating astrocytes of the Alzheimer's disease brain. Am J
Pathol. Mar 2006;168(3):936-946.
[49] Missler U, Wiesmann M, Wittmann G, Magerkurth O, Hagenstrom H. Measurement of
glial fibrillary acidic protein in human blood: analytical method and preliminary
clinical results. Clin Chem. Jan 1999;45(1):138-141.
[50] Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus
S100B in serum after traumatic brain injury: relationship to brain damage and
outcome. J Neurotrauma. Nov 2004;21(11):1553-1561.
[51] Pelinka LE, Kroepfl A, Schmidhammer R, et al. Glial fibrillary acidic protein in serum
after traumatic brain injury and multiple trauma. J Trauma. Nov 2004;57(5):1006-
1012.
[52] van Geel WJ, de Reus HP, Nijzing H, Verbeek MM, Vos PE, Lamers KJ. Measurement
of glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta. Dec
2002;326(1-2):151-154.
[53] Nylen K, Ost M, Csajbok LZ, et al. Increased serum-GFAP in patients with severe
traumatic brain injury is related to outcome. J Neurol Sci. Jan 15 2006;240(1-2):85-91.
[54] Stiell IG, Wells GA. Methodologic standards for the development of clinical decision
rules in emergency medicine. Ann Emerg Med. Apr 1999;33(4):437-447.
[55] Laupacis A, Sekar N, Stiell IG. Clinical prediction rules. A review and suggested
modifications of methodological standards. Jama. Feb 12 1997;277(6):488-494.
[56] Carey ME. Analysis of wounds incurred by U.S. Army Seventh Corps personnel
treated in Corps hospitals during Operation Desert Storm, February 20 to March
10, 1991. J Trauma. Mar 1996;40(3 Suppl):S165-169.
Proteomics – Human Diseases and Protein Functions
106
[57] Sapsford W. Penetrating brain injury in military conflict: does it merit more research? J
R Army Med Corps. Mar 2003;149(1):5-14.
[58] Okie S. Traumatic brain injury in the war zone. N Engl J Med. May 19
2005;352(20):2043-2047.




Addendum: Common correlation with physiological symptoms and disease states.


                                  Pain     Fatigue Mood Digest       Sleep
Underhydration                    P        P            P            P
Food sensitivities                P        P       P    P            P
Joint subluxations                P        P
Radiculopathies                   P        P
Myelopathy                        P        P       P    P            P
Viscerosomatic reflex             P
Infectious malaise                P        P        P
Arthritides                       P
Low bone densitiy          P   P
Hypovitaminosis D          P   P   P       P
Calcium deficiency         P   P       P   P
Iron deficiency                P           P
Magnesium deficiency       P   P           P
Tyrosine deficiciency      P   P   P       P
Fatty acid deficiency              P       P
Zinc deficiency                        P
Hypoadrenia                P   P   P       P
Hyperadrenia                   P   P   P   P
AAT deficiency             P   P
Poor posture               P   P
Parasite infection         P   P       P   P
Non-restorative sleep      P   P   P
Metal toxicity                 P   P
Candidiasis                P   P       P
Dysbiosis                              P
Dysglycemia                    P   P       P
Hyponatremia                   P   P
Anemia                         P
Hypothyroid                    P   P   P   P
Functional acidosis            P       P
Foreign energies                   P
Zeta virus                         P
Pancreatic insufficiency               P
H. pylori infection                    P
Hypochlorhydria                        P
Prolapsed colon                        P
Hiatal hernia                          P
Rib torque                             P
Medication side-effects    P           P   P
Retless legs                               P
Meridian dysfunction                       P
Light & sound dysruption                   P
Poor stress management     P   P   P   P   P

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White paper

  • 1. White Paper 13 March 2013 Innoception Technologies LLC is pioneering an Integrative Health platform for untethered measurement of health parameters for an online, cloud-based format. This platform combines off-the-shelf and proprietary technologies from a recently successful crowdsourcing effort to produce a reliable, consistent process that quantizes wellness. This collaboration brings the most progressive available technologies together on a platform that will allow the customer to track his/her health in a dynamic and accurate online way. It has been surmised for some time that there is an optimum range of physiological functioning that will allow health providers unprecedented accuracy in assigning customers to wellness profiles across demographic and diagnostic groups. Our approach to capturing this neurophysiological state takes into account the diversity of the human species, reflecting the genomic adaptability that explains our success on this planet. Revealing physiological baseline information in a dynamic context goes beyond the understanding of traditional medicine in regards to disease management to a predictive one that emphasizes the importance of returning the individual to his/her optimum physiological baseline. Operating within their unique parameters will make possible their most efficient use of medical interventions and allow quick rehabilitation and recovery from health challenges of all kinds. This approach will also reveal new information about global wellness issues like immune system functioning and recovery, since the immune system’s optimum functioning is the true key to lifelong wellness. This paper presents an overview of the collaborative roles that will allow this approach to Integrative Health and wellness to succeed and give a concise and integrative view of the true promise of personalized health. This paper discusses the format for this ongoing enquiry along with the market forces which affect the adoption of a new approach to health that emphasizes wellness. A unique collaboration among several existing businesses and their proprietary technologies will allow this effort to proceed. Also, the location at the University of Utah will give access to critical resources for genomic enquiry and data management that exist nowhere else. Innoception Technologies LLC is a Medical Technology startup licensed at the University of Utah Technology Commercialization Office. We are unique in having a broad support base across five major departments at the U/U. We have two specific patents licensed to us that offer us impressive market advantages. One is a
  • 2. process patent for concurrent measurement of biosignals during a therapeutic or medical intervention. Another is a unparalleled approach to ‘big data,’ “NDV” or n-dimensional visualization developed by the head of our science advisory board and former head of Computer Science at the U/U, Robert Johnson PhD. Analysis of biosignals with their orthogonal fields adds to the specificity and sensitivity of accurate diagnostic formulations. Individuals within our team have been measuring patterns made by the brain/body’s physiological subsystems since 2005. We have rediscovered the nonlinear nature of biological systems, where system output is not a straight line function of its input. Nonlinear systems are both stable and flexible as they go about task performance. We have chosen three physiological signals that fluctuate orthogonally to each other, allowing us to define a “corridor of normal”, age and sex specific, for each biosignal, where individual clinical conditions fall outside this corridor in characteristic ways. On a small scale, many studies have shown the utility of applying multivariate analysis and data mining techniques to medical data. Innoception’s approach will be unique for examining the collective effect of many parameters for relevance to health disorders. Multiparameter analysis (MPA) techniques include vector fusion, Shannon information analyses and other topological data mining approaches. These are expected to indicate how specific groups of bio-signal parameters collectively enhance or diminish correlation patterns with specific neurophysiological states associated with anxiety disorders, for example. Development of effective MPA methods, using archived data when possible, will be the focus during the first year. Standard statistical approaches in medical research are generally too limited to appreciate the physiological diversity that determines lifelong wellness. The challenges of capturing optimum human functioning are also the challenges of ‘big data’ and in the future, HIPAA-related concerns for data capture and maintenance will not only focus on patient protection but also the ability to maintain the Value of Information (VOI). As a part of healthcare reform, many health stakeholders are grappling at present with the portability of information across HIEs (Health Information Exchanges) where most traditional health entities are for the first time addressing core empirical issues in terms of how meaningful health data is captured and maintained in the context of personalized healthcare and the integration of dissimilar data sources. The proposed collaboration will result in a ‘best practices’ model since biophysiological data will be analyzed across a spectrum of integrative health interventions which evidence the greatest therapeutic benefit in these conditions. Then healthy information will lead to a greater variety of choices for the healthcare consumer and
  • 3. allow a collaborative approach to health. Biopsychosocial phenomenon and social factors dynamically interact and affect the individual’s ability to adapt. The most promising therapies for traumatically induced biophysiological conditions are often integrative and holistic approaches to symptom management. I. Traumatic experience, disability and Health Events: The heart receives neural stimulation from both the sympathetic and parasympathetic ANS components. Blood pressure regulation is one of the most important ANS functions. Baroreceptor cells in the heart and blood vessels sense pressure and send afferent signals to the brain where components of the ANS that control heart rate and vascular tonus via sympathetic, and to a lesser extent parasympathetic, activity. This is a dedicated feedback control system to maintain blood pressure within proper limits by adjusting heart rate and cardiac output in response to environmental and emotional influences. Thus heart rate is recognized as a basic measure of ANS function. Other factors affecting cardiac regulation include respiration, thermoregulation, and humoral regulation, whose ANS influences also reflect neurophysiological status is subtle ways. The cardiovascular bio-signal parameters briefly described below reflect various aspects of ANS activity; they will be studied using multiparameter analysis for relevancy as potential individual or clustered markers for anxiety disorders. Blood Pressure Heart Rate (HR) High resting heart rate is also associated with increased risks of adverse outcomes for coronary artery disease (CAD). Heart Rate Variability (HRV) is an important parameter for reflecting ANS status. Physiologically, a significant increase in HF/LF power, followed by a sharp decrease is cited as a predictor of paroxysmal atrial fibrillation (PAF), and low HRV reflects poor cardiac health. Complicating issues include HRV reflection of both sympathetic and parasympathetic activity, and significant HRV differences are commonly found between individuals. P-wave dispersion and variability have been the focus of several recent research studies. The Q- T interval A technique using root-mean square values across multiple ECG leads has been used at the University of Utah to obtain reliable Q-T intervals for research projects. QT dispersion may
  • 4. be associated with increased risks of arrhythmic events and syncope, and it may predict sudden cardiac death in variety of disease states such as acute myocardial infarction and hypertrophic cardiomyopathy. Respiratory Sinus Arrhythmia (RSA) is related to the HF peak in the HRV spectrum and it primarily indicates parasympathetic ANS activation Baroreflex sensitivity (BRS) associates reduced parasympathetic function with PTSD in males, but a recent study found contrary gender effects in BRS among smokers. Vagal tone is a positive indicator of stress and is considered important parameters for characterizing anxiety disorders. The characteristics of these bio-signals will be studied and classified quantitatively as potential contributors for developing multiparameter bio-signal marker patterns for neurophysiological conditions and states such as anxiety disorders. 1.- ECG 2.- Diastolic Blood Pressure (DBP) 3.- Systolic Blood Pressure (SBP) 4.- Glucose Test (GT) 5 .- Average glucose for the past 8 weeks test (H1A1c Test) 6.- Type of medication used. 7.- High Density Lipoprotein (HDL) 8.- Low Density Lipoprotein (LDL) 9.- Weight (WT) 10,- Fast Plasma Glucose test 11.- Body mass Index (BMI) We will be seeking to additionally develop new areas where the analysis methods and data mining approaches we possess offer great promise. For example, In 2000, according to the World Health organization (WHO), at least 171 million people or 2.8% of the population suffered from diabetes. The number is increasing rapidly, and by 2030, the number will double. Type 2 diabetes is more common in the Western world, where urbanization and lifestyle changes have increased the prevalence of the illness, and an environmental (dietary) affect is implied. Type 2 affects up to 95% of the US diabetes population. 18.6% of those above 60 have diabetes, from the National
  • 5. Health and Nutrition Examination Survey. In particular, the system we propose specifically predicts the diabetes variables of a patient for the next scheduled doctor’s visit. Alarming values in these predictions can trigger automatic warnings to the medical professional allowing for scheduling more frequent visits, which allows the medical professional to timely intervene. To predict the future diabetes variables from past data, we propose to use artificial intelligence and machine learning techniques. Our algorithms will be trained on the existing rich set of patient data in the Utah diabetes database. Various AI and ML techniques are candidates to be adapted to successfully achieve this goal. One approach would be to view the patient as a dynamical system, whose dynamics equations (governing the evolution of its state over time) are unknown. Various AI and ML techniques exist to learn these dynamics equations from past data. Given such a dynamics model, it can readily be used to predict the patient’s state into the future, and it is able to provide a measure of (un)certainty about its prediction. Another class of techniques builds on Artificial neural networks (ANN), which is a powerful empirical pattern-recognition and mapping tool for different data, including approximation of complex nonlinear relationships, as well as different outcomes that characterize individualized epidemiological trajectories. In personalized healthcare, these trajectories are revealed as epigenetic influences accompanied by discrete medical indicators. Instead of imposing an a priori model on the data, ANN learns input and output relationships directly from the data. The flexibility of the ANN models has led to successful application in population pharmacokinetic and pharmacodynamic data analysis. Standard medical information and local clinical studies will be related to one or more conventional psychiatric scale metrics such as the Hamilton Anxiety Scale, Hamilton Depression Scale, Positive and Negative Syndrome Scale, Clinician-administered PTSD Scale, Mississippi Scale for Combat-Related PTSD, and Watson's criteria for PTSD in the veteran arms of the studies. This provides well documented classification references for each bio-signal record. Local clinical studies are planned for the second year to verify MPA results. Laboratory serum assays will be collected to determine the levels of stress markers such as cytokines and chemokines to further verify the results through multiparameter analysis techniques. Lastly, since the ECG inherently reflects many aspects of the heart’s physical status, it is possible that in the process of mining neurological information from ECG parameters, Innoception may also uncover new marker patterns for certain cardiovascular conditions. This possibility is considered a secondary facet of the proposed research project, and relevant discoveries in the cardiovascular
  • 6. areas will be documented for further investigation. It should be observed that A-Fib and other chronic heart conditions may have a higher incidence in veteran populations than in the general population. Innoception will develop and employ multiparameter analysis techniques in a structured investigation of complex bio-signal parametric relationships associated with anxiety disorders in the ECG bio-signal. As progress is made in discovering collective ECG parameter correlations to anxiety traits, additional bio-signal parameters from other bio-signals, such as blood pressure, and skin conductance will be included in the study to develop a multi-modal approach for objective neurological state analysis. II. Collaborators Drs Ed Fila and Regina Drueding (co-founders) have been pioneers and successful entrepreneurs in CVD prevention and CIMT development. They, in prior entities, developed the CIMT software that received FDA approval, sold to an ultrasound manufacturer, and established several CIMT outsourcing companies that today are the primary industry players. Dr. Fila has also been intimately involved in researching cancer prevention (including researching facilities or practitioners getting exceptional results), treating depression, getting metals out of the body, reducing effects of radiation, etc. (all major drivers of CVD), A seasoned corporate executive, Fortune 500 consultant and entrepreneur, Bruce Collett will lead the effort to establish cardiovascular measurement with this technology. Two other founders contribute engineering, QC, project management, IT systems, marketing and business skills. Tomasz Petelenz PhD and Robert Tuckett PhD will guide the bioengineering aspects of the project, both with extensive experience in the assessment and measurement of relevant physiological parameters that relate to health and wellness. Proprietary technologies that will be utilized include biochemical analysis of the breath, developed by Royce Johnson PhD, and the use of blood markers to quantize the neurological level of functioning/injury developed by Banyan Pharma. We feature the combination of these new technologies that we consider critical to the capture of a meaningful and accurate dynamic measurement of physiological baseline and will actively collaborate with them in utilizing these proprietary technologies on the Innoception platform. Breath analysis for health diagnosis and management: The principle long-term target for EZKnowz™ is for health diagnosis and health management, through breath or odor analysis. We all know that the “elephant in the room” is the extremely high cost of healthcare and that current proposed solutions are not adequate. In search of fresh approaches, it worth noting that the computer technology industry is one of the few industries where the cost becomes lower year after year, driven by Moore’s Law, where
  • 7. computer power doubles every 18 months. Creative coupling of this digital power offers a chance to rein in the spiraling cost of healthcare. The question is: What is the optimal way of implementation of computing power and internet communication in the healthcare industry? One great possibility of healthcare cost reduction is to find a solution to “the fact that much time and money is spent on patients visiting their doctors or a clinic and too little attention is afforded to preventive care”. Improvements in preventive diagnostics will help reduce hospital admission costs and allow patients to be cared for at home, for longer. The biggest issue is keeping patients out of hospitals. Simple diagnostic devices are needed that operate at the personal level and that can universally monitor the health status of individuals in a home environment in real time. These diagnostic devices should be able to digitize the collected information and use the internet to transfer data and communicate with the doctor’s offices. Powerful consumer gadgets already exist that are simple to use and consistent with the existing PCs infrastructure, whether this is smart phone, IPad, a notebook, etc. Our vision is to emulate the IT/PC revolution by empowering the individuals with digital, personal, real time monitoring devices for the purpose of preventive care and facilitating early diagnostics. why we cannot communicate with doctors without face to face meetings, and there is no reason that preventive care should not have excellent remote medical coverage. We and many others believe that there is a huge business opportunity here! For example, one study has identified as many as 3,481 components in human breath. Already correlations between increases in specific components (markers) with physiological sources and conditions have been identified (lung cancer, influenza, tuberculosis, etc.). Advantages are:  Non-invasive (painless),  Sample is easy acquire,  Information rich,  Digital information available immediately,  Low-cost and easy to administer. Patented claims to protect these concepts and the first issued claims are published in “Analysis of Gases” (Issued European Patent EP 1 976 431 B1). Use of biomarkers in neurological functioning/injury. Although there are a number of biochemical markers that have been investigated in TBI, our discussion will include the most current and widely studied ones. The most extensively studied among these are glial protein S-
  • 8. 100 beta(β) 45-55, neuron-specific enolase (NSE)56-63, and myelin basic protein (MBP)41, 59, 64-66 Although some of these published studies suggest that these biomarkers correlate with degree of injury; conflicting results exist (3-11). S100β is the major low affinity calcium binding protein in astrocytes (3) and it is considered a marker of astrocyte injury or death. It can also be found in non-neural cells such as adipocytes, chondrocytes, and melanoma cells (12). Elevated serum levels have been associated with increased incidence of post concussive syndrome and impaired cognition (13,14). Other studies have reported that serum levels of S-100β are associated with MRI abnormalities and with neuropsychological examination disturbances after mild TBI (15,16). A number of studies have found significant correlations between elevated serum levels of S-100β and CT abnormalities (17-19). It has been suggested that adding the measurement of S-100B concentration to clinical decision tools for mild TBI patients could potentially reduce the number of CT scans by 30%.84 Other investigators have failed to detect associations between S-100β with CT abnormalities (3,20-22). The vast majority of these clinical studies have employed ELISA to measure levels of S100B. Although S-100β continues to be actively investigated and remains promising as an adjunctive marker, its utility as a biochemical diagnostic remains controversial. Some studies have observed high serum S-100β levels in trauma patients without head injuries suggesting that it lacks CNS specificity and is released from peripheral tissues (23-25). Neuron specific enolase is one of the five isozymes of the gycolytic enzyme enolase found in central and peripheral neurons and it has been shown be elevated following cell injury (26). It has a molecular weight of 78 kDa and a biological half-life of 48 hours (27). This protein is passively released into the extracellular space only under pathological conditions during cell destruction. Most studies employed an enzyme immunoassay for NSE detection. Many of these studies either contained inadequate control groups or concluded that serum NSE had limited utility as a marker of neuronal damage. Early levels of NSE and MBP concentrations have been correlated with outcome in children, particularly those under 4 years of age(1,2,28,29). A limitation of NSE is the occurrence of false positive results in the setting of hemolysis (30). A supposedly cleaved form of tau, c-tau, has also been investigated as a potential biomarker of CNS injury. Tau is preferentially localized in the axon and tau lesions are apparently related to axonal disruption (31,32). CSF levels of c-tau were significantly elevated in TBI patients
  • 9. compared to control patients and these levels correlated with clinical outcome (33,34). Though levels of c-tau were also elevated in plasma from patients with severe TBI, there was no correlation between plasma levels and clinical outcome. A major limitation of all of these biomarkers is the lack of specificity for defining neuropathological cascades. Using the same proteomic Western blot technique, levels of spectrin breakdown products (SBDP’s) have been reported in CSF from adults with severe TBI and they have shown a significant relationship with severity of injury and clinical outcome (35-40). Following a TBI the axonally enriched cytoskeletal protein -II-spectrin is proteolyzed by calpain and caspase-3 to signature breakdown products (SBDPs). Calpain and caspase-3 mediated SBDP levels in CSF have shown to be significantly increased in TBI patients at several time points after injury, compared to control subjects. The time course of calpain mediated SBDP150 and SBDP145 (markers of necrosis) differs from that of caspase-3 mediated SBDP120 (marker of apoptosis). A promising candidate biomarker for TBI currently under investigation is Ubiquitin Cterminal Hydrolase-L1 (UCH-L1). UCH-L1 was previously used as a histological marker for neurons due to its high abundance and specific expression in neurons (41). This protein is involved in the addition and removal of ubiquitin from proteins that are destined for metabolism (42). It has an important role in the removal of excessive, oxidized or misfolded proteins during both normal and pathological conditions in neurons (43). In initial studies, UCH-L1 was identified as a protein with a two-fold increase in abundance in the injured cortex 48 hours after controlled cortical impact in a rat model of TBI (44). Subsequently, a UCH-L1 sandwich enzyme-linked immunosorbent assay quantitatively showed that CSF and serum UCH-L1 levels in rats were significantly elevated as early as 2 hours following both traumatic and ischemic injury (45). Clinical studies in humans with severe TBI confirmed, using ELISA analysis, that the UCH-L1 protein was significantly elevated in human CSF44 (46), and was detectable very early after injury and remained significantly elevated for 168 hours post- injury. Further studies in severe TBI patients have revealed a very good correlation between CSF and serum levels. Most recently, UCH-L1 was detected in the serum of mild and moderate TBI (MMTBI) patients within an hour of injury. Serum levels of UCH-L1 discriminated MMTBI patients from uninjured and non-head injured trauma controls and were also able to distinguish mild TBI (concussion patients) from these controls. Most notable was that levels were significantly higher in those with intracranial lesions on CT than those without lesions. Glial
  • 10. Fibrillary Acidic Protein (GFAP) is a monomeric intermediate protein found in astroglial skeleton that was first isolated by Eng et al. in 1971. GFAP is found in white and gray brain matter and is strongly upregulated during astrogliosis. Current evidence indicates that serum GFAP might be a useful marker for various types of brain damage from neurodegenerative disorders (47,48) and stroke to severe traumatic brain injury (49-53). Clinical researchers have developed methodological standards for developing clinical decision tools in order to ensure the validity of study results (54,55). As TBI biomarker research transitions from the bench to the bedside there are a number of important methodological issues that researchers will have to consider as they design their clinical protocols. Since TBI biomarkers are being designed for clinical management, the outcome or diagnosis being examined will need to be clearly defined and clinically important. In order to ensure external validity and the generalizability of the results, study patients will have to be selected without bias and represent a wide spectrum of clinical and demographic characteristics. When interpreting the data, clinical variables that potentially affect outcome will require careful consideration in the analysis. Biochemical markers could help with clinical decision making by elucidating injury severity, injury mechanism(s), and monitoring progression of injury. Temporal profiles of changes in biomarkers could guide timing of diagnosis and treatment. Biomarkers could have a role in management decisions regarding patients at high risk of repeated injury. Accurate identification of these patients could facilitate development of guidelines for return to duty, work or sports activities and also provide opportunities for counseling of patients suffering from these deficits. Repeated mild TBI occurring within a short period (i.e. hours, days, or weeks) can be catastrophic or fatal, a phenomenon termed ‘second impact syndrome.’ Acute CT or MRI abnormalities are not usually found after these injuries, but levels of some neurotransmitters remain elevated, and a hypermetabolic state may persist in the brain for several days after the initial injury. Biomarkers could serve as prognostic indicators by providing information for patients and their families about the expected course of recovery. It opens the door to the initiation of early therapies. Identifying at-risk patients with less apparent TBI or differentiating injury pathology in those with more severe intracranial processes would be tremendously valuable in the management of these patients. For example, in a patient with a normal CT scan or MRI, a
  • 11. biomarker that could predict worsening neurological status or long-term disability would have great clinical utility. There have been a large number of clinical trials studying potential therapies for traumatic brain injury (TBI) that have resulted in negative findings. Biomarkers measurable in blood would have important applications in clinical research of these injuries. Biomarkers could provide clinical trial outcome measures that are cost-effective and more readily available than conventional neurological assessments, thereby significantly reducing the risks and costs of human clinical trials. Biomarkers that represent highly sensitive and specific indicators of disease pathways have been used as substitutes for outcomes in clinical trials when evidence indicates that they predict clinical risk or benefit. Lack of quickly accessible pathophysiologic information during the post-injury course has made pharmacologic intervention problematic. Biomarkers could provide more timely information on disease progression and the effects of interventions such as drugs and surgery. Biomarker measurements could potentially relate the effects of interventions on molecular and cellular pathways to clinical responses. In doing so, biomarkers would provide an avenue for researchers and clinicians to gain a mechanistic understanding of the differences in clinical response that may be influenced by uncontrolled variables. Intoxicated, unconscious, sedated, or polytraumatized patients suspected of having a TBI pose a particular challenge to emergency and trauma physicians. Biomarkers could expedite the evaluation of such patients by providing information on the degree of brain injury prior to neuroimaging. Biomarkers in this setting could also help determine the need for early neurosurgical consultation or transfer to facilities with neurosurgical capabilities. There are potential military applications as well. Serum biomarkers could help diagnose and/or triage brain injured military servicemen and women. TBI is a leading cause of combat casualty with an estimated 15-20% of all injuries sustained in 20th century conflicts being to the head (57-58). America's armed forces are sustaining attacks by rocket-propelled grenades, improvised explosive devices, and land mines almost daily in the recent conflicts in Iraq and Afghanistan.145 It has been suggested that over 50% of injuries sustained in combat are the result of such explosive munitions including bombs, grenades, land mines, missiles, and mortar/artillery shells. Neuroimaging techniques to diagnose brain injury acutely and other monitoring tools that assess secondary insults are not immediately available in combat zones and
  • 12. such casualties have to be evacuated. Triage and management of brain injured soldiers could be significantly improved if first responders had a quick and simple means of objectively assessing severity of brain injury and of monitoring secondary insults. There is a unique opportunity to use the insight offered by biochemical markers to shed light on the complexities of the injury process. Accordingly, certain markers could be used as indicators of damage to a particular cell type or cellular process or may be indicative of a particular type of injury. Neuroanatomically, that could include evidence of, say, primary axonal damage versus glial damage. With such heterogeneity the solution may not lie with a single biomarker but more with a complementary panel of markers that may prove useful in distinguishing different pathoanatomic processes of injury. III. Development of Healthbooks™ In the business model using software as a service (SaaS), users are provided access to application software and databases. The cloud providers manage the infrastructure and platforms on which the applications run. SaaS is sometimes referred to as “on-demand software” and is usually priced on a pay- per-use basis. SaaS providers generally price applications using a subscription fee. • Proponents claim that the SaaS allows a business the potential to reduce IT operational costs by outsourcing hardware and software maintenance and support to the cloud provider. This enables the business to reallocate IT operations costs away from hardware/software spending and personnel expenses, towards meeting other IT goals. In addition, with applications hosted centrally, updates can be released without the need for users to install new software. One drawback of SaaS is that the users' data are stored on the cloud provider’s server. As a result, there could be unauthorized access to the data. End users access cloud-based applications through a web browser or a light-weight desktop or
  • 13. mobile app while the business software and user's data are stored on servers at a remote location. Proponents claim that cloud computing allows enterprises to get their applications up and running faster, with improved manageability and less maintenance, and enables IT to more rapidly adjust resources to meet fluctuating and unpredictable business demand. In the most basic cloud-service model, providers of IaaS offer computers - physical or (more often) virtual machines - and other resources. (A hypervisor, such as Xen or KVM, runs the virtual machines as guests. Pools of hypervisors within the cloud operational support-system can support large numbers of virtual machines and the ability to scale services up and down according to customers' varying requirements.) IaaS clouds often offer additional resources such as images in a virtual-machine image- library, raw (block) and file-based storage, firewalls, load balancers, IP addresses, virtual local area networks (VLANs), and software bundles. IaaS-cloud providers supply these resources on-demand from their large pools installed in data centers. For wide-area connectivity, customers can use either the Internet or carrier clouds (dedicated virtual private networks).
  • 14. Cloud computing relies on sharing of resources to achieve coherence and economies of scale similar to a utility (like the electricity grid) over a network. At the foundation of cloud computing is the broader concept of converged infrastructure and shared services. The underlying concept of cloud computing dates back to the 1950s, when large-scale mainframe became available in academia and corporations, accessible via thin clients / terminal computers. To make more efficient use of costly mainframes, a practice evolved that allowed multiple users to share both the physical access to the computer from multiple terminals as well as to share the CPU time. This eliminated periods of inactivity on the mainframe and allowed for a greater return on the investment. The practice of sharing CPU time on a mainframe became known in the industry as time-sharing. In the 1990s, telecommunications companies, who previously offered primarily dedicated point-to-point data circuits, began offering virtual private network (VPN) services with comparable quality of service but at a much lower cost. By switching traffic to balance utilization as they saw fit, they were able to utilize their overall network bandwidth more effectively. The cloud symbol was used to denote the demarcation point between that which was the responsibility of the provider and that which was the responsibility of the users. Cloud computing extends this boundary to cover servers as well as the network infrastructure. As computers became more prevalent, scientists and technologists explored ways to make large-scale computing power available to more users through time sharing, experimenting with algorithms to provide the optimal use of the infrastructure, platform and applications with prioritized access to the CPU and efficiency for the end users. Gathering data is a fairly easy task, understanding it is the problem. Big data presents a challenge in that the value of information (VOI) becomes a key consideration- allowing the meaning of medical data to the patient will be considered a HIPAA violation in the furue. Today we rely heavily on digital data streams to analyze everything from the timing microwave ovens to listening to music from an iPhone. One characteristic of digital data is that is very mundane – it is very much like Morse code. At least in Morse code there was a long sound and a short sound. maybe even some rhythm Some very adept in Morse code could understand the various clicks as a language. Digital data would not be very practical without a computer. - imagine reading this document in Morse code! Fortunately, modern fast computers exist to eliminate that boredom..
  • 15. Let's look at our objective: Provide a improved quality of life through a few simple, unobtrusive devices that provide a constant stream of digital data concerns our current health status. One, unusual, benefit of constant health monitoring is now we will now what is right. If you are flying North and you have a cross wind to the West it is obvious – to correct - one needs to fly a little bit East. The key is a constant data stream that is routinely interpreted for all aspects of health – those that are bad, those that are good and all those in between. Collected data is then normalized for each individual that can be compared to the general populace instead of the other way around. Once a data stream is collected it can then be easily transformed to be easily understood much like this document had be transformed from Morse code. HIPAA compliance requires that the architecture of the system be designed for failure- not just the interruption of the data-architecture but the loss of connections that are essential to preserve the meaning of the data. Failure to decouple the links between the applications and the sources of data, especially when they are likely to be so numerous, would be catastrophic. Applications must not be designed to expect data, especially transient data, but the application and the device must be expected to intercommunicate—but to execute completely independent of each other. A last example to
  • 16. consider is the accelerating pace of business itself. Back-office systems have been designed and built for years to run with extremely high performance and throughput. These back-office systems have been measured by transactions per second, and response times to the submission of an individual piece of work. As teams move to accessing and even running these solutions outside the enterprise, they continue to expect the reliability and the speed of response seen within the enter-prise domain. To try to achieve this will require substantial evaluation of how to implement this connectivity to try to balance these requests. When it comes to responding to requests, delays of even a second or more may lead to users to believe that there is be a problem, and a negative perception can lead to rapid dissatisfaction with the solution. The growth of cloud computing has created a change in this picture. Cloud is not a single thing, but in fact can be used to describe the more-dynamic allocation and use of in-house IT resources, or cloud can mean the use as needed of publically available IT resources on a usage-based model. Or cloud could be any combination of these—and even other—deployment types. Business leaders are likely to be considering which of their IT systems, and which of their applications, are suitable for deployment in the cloud—whatever cloud might mean to them. Perhaps this might be for cost-saving reasons, or it might be for more flexible deployment in response to a growth in usage, or it might simply be the fastest way to get something done. Whatever the reason, applications will need to become ever more agnostic about their runtime environment, and the connections they have to the rest of the enterprise. They will need to be loosely connected, but reliably and securely connected, enabling business teams to make decisions on deployment completely independent of the application architecture itself. Applications and the business IT infrastructure itself needs to be robust enough, and must perform fast enough, to consume and take action on all the data and all the events, in a timely manner. Other data can be held and processed to extract the remaining value. Indeed, the applications and infrastructure must be both high-performing and “smart.” Applications and infrastructure must not only be able to recognize the data that was previously important, but must change to be able to identify and act upon some of the rest of the Big Data, creating the new business opportunities that Big Data represents, even while Big Data creates new challenges to the IT infrastructure—the systems, the applications and the connections between them. One final way to move data between applications is to use a dedicated middleware layer for enterprise messaging. This is a similar approach to the embedded JMS messaging mentioned above, but avoids the
  • 17. limitations of being Java only, and of only connecting to other instances running in the same application server environment. The enterprise messaging approach also avoids some of the limitations of HTTP, since you are able to use more loosely coupled requests, including both time- independence and transactional integrity. And although it is different from a file transfer solution, enterprise messaging can be used to enhance, replace or update an existing or a new file transfer-based approach without application disruption. As discussed above, many business leaders use applications coded in Java, running in an application server. Part of the Java standard is JMS—providing a messaging service as a part of the programming model. Using JMS is therefore a natural way for such applications to move data into an application and out of an application, and many application servers include a JMS provider to “listen” for JMS requests and execute them. However, this will only work if both the sending application and the receiving application are running a common JMS provider. Although JMS is a standard API, the wire format is not standard, so different JMS providers cannot exchange messages IV. Our corporate advantages for the researcher include:
  • 18. Alignment of Integrative Health with disciplines that focus on human stress/resilience makes alignment with that community a high priority biosignal analysis for those involved in the development of these new technologies • Submission of grants through TCO (Technology Commercialization Office) avoids high administrative charges for grants submitted through OSP (Office of Sponsored Projects) by various University Departments • Innoception will aggressively approach funding sources that are not available to most Academic or Medical projects • Innoception creates a protected place for those involved in development and fielding of measurement technologies to fully mature their intellectual property, whether device, or curriculum focused, provides an accelerated path to market • Ongoing work in biosignal technology development has overlooked the complex adaptive system. We offer unique technological resources to enable the investigation of this potentially fruitful area of enquiry • Principles associated with Innoception have an established track record of years of involvement in the Integrative and Academic community with stable networks in Business and Allied Technologies References [1] Berger RP, Adelson PD, Pierce MC, Dulani T, Cassidy LD, Kochanek PM. Serum neuron-specific enolase, S100B, and myelin basic protein concentrations after inflicted and noninflicted traumatic brain injury in children. J Neurosurg. Jul 2005;103(1 Suppl):61-68. [2] Berger RP, Beers SR, Richichi R, Wiesman D, Adelson PD. Serum biomarker concentrations and outcome after pediatric traumatic brain injury. J Neurotrauma. Dec 2007;24(12):1793-1801. [3] Piazza O, Storti MP, Cotena S, et al. S100B is not a reliable prognostic index in paediatric TBI. Pediatr Neurosurg. 2007;43(4):258-264. [4] Martens P. Serum neuron-specific enolase as a prognostic marker for irreversible brain
  • 19. damage in comatose cardiac arrest surviviors. Acad Emerg Med. 1996;3:126-131. [5] Rainey T, Lesko M, Sacho R, Lecky F, Childs C. Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: results using a single (24h) time-point. Resuscitation. Mar 2009;80(3):341-345. [6] Bazarian JJ, Zemlan FP, Mookerjee S, Stigbrand T. Serum S-100B and cleaved-tau are poor predictors of long-term outcome after mild traumatic brain injury. Brain Inj. Jun 2006;20(7):759-765. [7] Watt SE, Shores EA, Baguley IJ, Dorsch N, Fearnside MR. Protein S-100 and neuropsychological functioning following severe traumatic brain injury. Brain Inj. Sep 2006;20(10):1007-1017. [8] Morochovic R, Racz O, Kitka M, et al. Serum S100B protein in early management of patients after mild traumatic brain injury. Eur J Neurol. Oct 2009;16(10):1112-1117. [9] Dirnagl U CI, and Moskowitz MA. Pathology of ischaemic stroke: an integrated view. TINS. 1999;22(9):391-397. [10] Laskowitz ea. Serum Markers of Cerebral Ischemia. Journal of Stroke and Cerebrovascular Diseases. 1998;7(4 (July-August)):234-241. [11] Roine ea. Neurological outcome after out-of-hospital cardiac arrest. Prediction by cerebrospinal fluid enzyme analysis. Arch Neurol. 1989;46:753-756. [12] Zimmer DB, Cornwall EH, Landar A, Song W. The S100 protein family: history, function, and expression. Brain Res Bull. 1995;37(4):417-429. [13] Ingebrigtsen T, Romner B. Management of minor head injuries in hospitals in Norway. Acta Neurol Scand. Jan 1997;95(1):51-55. [14] Waterloo K, Ingebrigtsen T, Romner B. Neuropsychological function in patients with increased serum levels of protein S-100 after minor head injury. Acta Neurochir (Wien). 1997;139(1):26-31; discussion 31-22. [15] Ingebrigtsen T, Romner B. Serial S-100 protein serum measurements related to early magnetic resonance imaging after minor head injury. Case report. J Neurosurg. Nov 1996;85(5):945-948. [16] Ingebrigtsen T, Waterloo K, Jacobsen EA, Langbakk B, Romner B. Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome. Neurosurgery. Sep
  • 20. 1999;45(3):468-475; discussion 475-466. [17] Ingebrigtsen T, Romner B, Marup-Jensen S, et al. The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. Brain Inj. Dec 2000;14(12):1047-1055. [18] Muller K, Townend W, Biasca N, et al. S100B serum level predicts computed tomography findings after minor head injury. J Trauma. Jun 2007;62(6):1452-1456. [19] Biberthaler P, Linsenmeier U, Pfeifer KJ, et al. Serum S-100B concentration provides additional information fot the indication of computed tomography in patients after minor head injury: a prospective multicenter study. Shock. May 2006;25(5):446-453. [20] Phillips JP, Jones HM, Hitchcock R, Adama N, Thompson RJ. Radioimmunoassay of serum creatine kinase BB as index of brain damage after head injury. Br Med J. Sep 20 1980;281(6243):777-779. [21] Rothoerl RD, Woertgen C, Holzschuh M, Metz C, Brawanski A. S-100 serum levels after minor and major head injury. J Trauma. Oct 1998;45(4):765-767. [22] Bechtel K, Frasure S, Marshall C, Dziura J, Simpson C. Relationship of serum S100B levels and intracranial injury in children with closed head trauma. Pediatrics. Oct 2009;124(4):e697-704. [23] Rothoerl RD, Woertgen C. High serum S100B levels for trauma patients without head injuries. Neurosurgery. Dec 2001;49(6):1490-1491; author reply 1492-1493. [24] Romner B, Ingebrigtsen T. High serum S100B levels for trauma patients without head injuries. Neurosurgery. Dec 2001;49(6):1490; author reply 1492-1493. [25] Anderson RE, Hansson LO, Nilsson O, Dijlai-Merzoug R, Settergen G. High serum S100B levels for trauma patients without head injuries. Neurosurgery. 2001;49(5):1272-1273. [26] Skogseid IM, Nordby HK, Urdal P, Paus E, Lilleaas F. Increased serum creatine kinase BB and neuron specific enolase following head injury indicates brain damage. Acta Neurochir (Wien). 1992;115(3-4):106-111. [27] Schmechel D, Marangos PJ, Brightman M. Neurone-specific enolase is a molecular marker for peripheral and central neuroendocrine cells. Nature. Dec 21-28 1978;276(5690):834-836. [28] Varma S, Janesko KL, Wisniewski SR, et al. F2-isoprostane and neuron-specific enolase
  • 21. in cerebrospinal fluid after severe traumatic brain injury in infants and children. J Neurotrauma. Aug 2003;20(8):781-786. [29] Bandyopadhyay S, Hennes H, Gorelick MH, Wells RG, Walsh-Kelly CM. Serum neuron-specific enolase as a predictor of short-term outcome in children with closed traumatic brain injury. Acad Emerg Med. Aug 2005;12(8):732-738. [30] Johnsson P, Blomquist S, Luhrs C, et al. Neuron-specific enolase increases in plasma during and immediately after extracorporeal circulation. Ann Thorac Surg. Mar 2000;69(3):750-754. [31] Kosik KS, Finch EA. MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum. J Neurosci. Oct 1987;7(10):3142-3153. [32] Higuchi M, Lee VM, Trojanowski JQ. Tau and axonopathy in neurodegenerative disorders. Neuromolecular Med. 2002;2(2):131-150. [33] Shaw GJ, Jauch EC, Zemlan FP. Serum cleaved tau protein levels and clinical outcome in adult patients with closed head injury. Ann Emerg Med. Mar 2002;39(3):254-257. [34] Zemlan FP, Jauch EC, Mulchahey JJ, et al. C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res. Aug 23 2002;947(1):131-139. [35] Cardali S, Maugeri R. Detection of alphaII-spectrin and breakdown products in humans after severe traumatic brain injury. J Neurosurg Sci. Jun 2006;50(2):25-31. [36] Papa L, D’Avella D, Aguennouz M, et al. Detection of Alpha-II Spectrin And Breakdown Products In Humans After Severe Traumatic Brain Injury [abstract]. Acad Emerg Med. May 2004;11(5). [37] Papa L, Lewis SB, Heaton S, et al. Predicting Early Outcome Using Alpha-II Spectrin Breakdown Products In Human CSF After Severe Traumatic Brain Injury [abstract]. Acad Emerg Med. May 2006;13(5 (Suppl 1)). [38] Papa L, Pineda J, Wang KKW, et al. Levels of Alpha-II Spectrin Breakdown Products in Human CSF and Outcome After Severe Traumatic Brain Injury [abstract]. Acad Emerg Med. May 2005;12(5 (Suppl 1)). [39] Farkas O, Polgar B, Szekeres-Bartho J, Doczi T, Povlishock JT, Buki A. Spectrin breakdown products in the cerebrospinal fluid in severe head injury--preliminary
  • 22. observations. Acta Neurochir (Wien). Aug 2005;147(8):855-861. [40] Mondello S, Robicsek SA, Gabrielli A, et al. alphaII-spectrin breakdown products (SBDPs): diagnosis and outcome in severe traumatic brain injury patients. J Neurotrauma. Jul 2010;27(7):1203-1213. [41] Jackson P, Thompson RJ. The demonstration of new human brain-specific proteins by high-resolution two-dimensional polyacrylamide gel electrophoresis. J Neurol Sci. Mar 1981;49(3):429-438. [42] Tongaonkar P, Chen L, Lambertson D, Ko B, Madura K. Evidence for an interaction between ubiquitin-conjugating enzymes and the 26S proteasome. Mol Cell Biol. Jul 2000;20(13):4691-4698. [43] Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerative disorders. Drug News Perspect. Jul-Aug 2007;20(6):365-370. [44] Kobeissy FH, Ottens AK, Zhang Z, et al. Novel differential neuroproteomics analysis of traumatic brain injury in rats. Mol Cell Proteomics. Oct 2006;5(10):1887-1898. [45] Liu MC, Akinyi L, Scharf D, et al. Ubiquitin C-terminal hydrolase-L1 as a biomarker for ischemic and traumatic brain injury in rats. Eur J Neurosci. Feb 2010;31(4):722- 732. [46] Siman R, Toraskar N, Dang A, et al. A panel of neuron-enriched proteins as markers for traumatic brain injury in humans. J Neurotrauma. Nov 2009;26(11):1867-1877. [47] Baydas G, Nedzvetskii VS, Tuzcu M, Yasar A, Kirichenko SV. Increase of glial fibrillary acidic protein and S-100B in hippocampus and cortex of diabetic rats: effects of vitamin E. Eur J Pharmacol. Feb 21 2003;462(1-3):67-71. [48] Mouser PE, Head E, Ha KH, Rohn TT. Caspase-mediated cleavage of glial fibrillary acidic protein within degenerating astrocytes of the Alzheimer's disease brain. Am J Pathol. Mar 2006;168(3):936-946. [49] Missler U, Wiesmann M, Wittmann G, Magerkurth O, Hagenstrom H. Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem. Jan 1999;45(1):138-141. [50] Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versus S100B in serum after traumatic brain injury: relationship to brain damage and outcome. J Neurotrauma. Nov 2004;21(11):1553-1561.
  • 23. [51] Pelinka LE, Kroepfl A, Schmidhammer R, et al. Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma. Nov 2004;57(5):1006- 1012. [52] van Geel WJ, de Reus HP, Nijzing H, Verbeek MM, Vos PE, Lamers KJ. Measurement of glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta. Dec 2002;326(1-2):151-154. [53] Nylen K, Ost M, Csajbok LZ, et al. Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome. J Neurol Sci. Jan 15 2006;240(1-2):85-91. [54] Stiell IG, Wells GA. Methodologic standards for the development of clinical decision rules in emergency medicine. Ann Emerg Med. Apr 1999;33(4):437-447. [55] Laupacis A, Sekar N, Stiell IG. Clinical prediction rules. A review and suggested modifications of methodological standards. Jama. Feb 12 1997;277(6):488-494. [56] Carey ME. Analysis of wounds incurred by U.S. Army Seventh Corps personnel treated in Corps hospitals during Operation Desert Storm, February 20 to March 10, 1991. J Trauma. Mar 1996;40(3 Suppl):S165-169. Proteomics – Human Diseases and Protein Functions 106 [57] Sapsford W. Penetrating brain injury in military conflict: does it merit more research? J R Army Med Corps. Mar 2003;149(1):5-14. [58] Okie S. Traumatic brain injury in the war zone. N Engl J Med. May 19 2005;352(20):2043-2047. Addendum: Common correlation with physiological symptoms and disease states. Pain Fatigue Mood Digest Sleep Underhydration P P P P Food sensitivities P P P P P Joint subluxations P P Radiculopathies P P Myelopathy P P P P P Viscerosomatic reflex P Infectious malaise P P P Arthritides P
  • 24. Low bone densitiy P P Hypovitaminosis D P P P P Calcium deficiency P P P P Iron deficiency P P Magnesium deficiency P P P Tyrosine deficiciency P P P P Fatty acid deficiency P P Zinc deficiency P Hypoadrenia P P P P Hyperadrenia P P P P AAT deficiency P P Poor posture P P Parasite infection P P P P Non-restorative sleep P P P Metal toxicity P P Candidiasis P P P Dysbiosis P Dysglycemia P P P Hyponatremia P P Anemia P Hypothyroid P P P P Functional acidosis P P Foreign energies P Zeta virus P Pancreatic insufficiency P H. pylori infection P Hypochlorhydria P Prolapsed colon P Hiatal hernia P Rib torque P Medication side-effects P P P Retless legs P Meridian dysfunction P Light & sound dysruption P Poor stress management P P P P P