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White paper

  1. 1. White Paper 13 March 2013Innoception Technologies LLC is pioneering an Integrative Health platform for untetheredmeasurement of health parameters for an online, cloud-based format. This platform combinesoff-the-shelf and proprietary technologies from a recently successful crowdsourcing effort toproduce a reliable, consistent process that quantizes wellness. This collaboration brings the mostprogressive available technologies together on a platform that will allow the customer to trackhis/her health in a dynamic and accurate online way.It has been surmised for some time that there is an optimum range of physiological functioningthat will allow health providers unprecedented accuracy in assigning customers to wellnessprofiles across demographic and diagnostic groups. Our approach to capturing thisneurophysiological state takes into account the diversity of the human species, reflecting thegenomic adaptability that explains our success on this planet. Revealing physiological baselineinformation in a dynamic context goes beyond the understanding of traditional medicine inregards to disease management to a predictive one that emphasizes the importance of returningthe individual to his/her optimum physiological baseline. Operating within their uniqueparameters will make possible their most efficient use of medical interventions and allow quickrehabilitation and recovery from health challenges of all kinds. This approach will also revealnew 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 paperpresents an overview of the collaborative roles that will allow this approach to Integrative Healthand wellness to succeed and give a concise and integrative view of the true promise ofpersonalized health.This paper discusses the format for this ongoing enquiry along with the market forces whichaffect the adoption of a new approach to health that emphasizes wellness. A unique collaborationamong several existing businesses and their proprietary technologies will allow this effort toproceed. Also, the location at the University of Utah will give access to critical resources forgenomic enquiry and data management that exist nowhere else. Innoception Technologies LLC isa Medical Technology startup licensed at the University of Utah Technology CommercializationOffice. 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. 2. process patent for concurrent measurement of biosignals during a therapeutic or medicalintervention. Another is a unparalleled approach to ‘big data,’ “NDV” or n-dimensionalvisualization developed by the head of our science advisory board and former head of ComputerScience at the U/U, Robert Johnson PhD. Analysis of biosignals with their orthogonal fields addsto the specificity and sensitivity of accurate diagnostic formulations. Individuals within our teamhave 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 astraight line function of its input. Nonlinear systems are both stable and flexible as they go abouttask performance. We have chosen three physiological signals that fluctuate orthogonally to eachother, 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 datamining techniques to medical data. Innoception’s approach will be unique for examining thecollective effect of many parameters for relevance to health disorders. Multiparameter analysis(MPA) techniques include vector fusion, Shannon information analyses and other topologicaldata mining approaches. These are expected to indicate how specific groups of bio-signalparameters collectively enhance or diminish correlation patterns with specific neurophysiologicalstates 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 statisticalapproaches in medical research are generally too limited to appreciate the physiological diversitythat determines lifelong wellness. The challenges of capturing optimum human functioning arealso the challenges of ‘big data’ and in the future, HIPAA-related concerns for data capture andmaintenance will not only focus on patient protection but also the ability to maintain the Value ofInformation (VOI). As a part of healthcare reform, many health stakeholders are grappling atpresent with the portability of information across HIEs (Health Information Exchanges) wheremost traditional health entities are for the first time addressing core empirical issues in terms ofhow meaningful health data is captured and maintained in the context of personalized healthcareand the integration of dissimilar data sources. The proposed collaboration will result in a ‘bestpractices’ model since biophysiological data will be analyzed across a spectrum of integrativehealth interventions which evidence the greatest therapeutic benefit in these conditions. Thenhealthy information will lead to a greater variety of choices for the healthcare consumer and
  3. 3. allow a collaborative approach to health. Biopsychosocial phenomenon and social factorsdynamically interact and affect the individual’s ability to adapt. The most promising therapies fortraumatically induced biophysiological conditions are often integrative and holistic approaches tosymptom management. I. Traumatic experience, disability and Health Events:The heart receives neural stimulation from both the sympathetic and parasympathetic ANScomponents. 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 thebrain 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 tomaintain blood pressure within proper limits by adjusting heart rate and cardiac output inresponse to environmental and emotional influences. Thus heart rate is recognized as a basicmeasure of ANS function. Other factors affecting cardiac regulation include respiration,thermoregulation, and humoral regulation, whose ANS influences also reflect neurophysiologicalstatus is subtle ways.The cardiovascular bio-signal parameters briefly described below reflect various aspects of ANSactivity; they will be studied using multiparameter analysis for relevancy as potential individualor clustered markers for anxiety disorders.Blood PressureHeart Rate (HR) High resting heart rate is also associated with increased risks of adverseoutcomes 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 apredictor 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 atthe University of Utah to obtain reliable Q-T intervals for research projects. QT dispersion may
  4. 4. be associated with increased risks of arrhythmic events and syncope, and it may predict suddencardiac death in variety of disease states such as acute myocardial infarction and hypertrophiccardiomyopathy.Respiratory Sinus Arrhythmia (RSA) is related to the HF peak in the HRV spectrum and itprimarily indicates parasympathetic ANS activationBaroreflex 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 forcharacterizing anxiety disorders.The characteristics of these bio-signals will be studied and classified quantitatively as potentialcontributors for developing multiparameter bio-signal marker patterns for neurophysiologicalconditions and states such as anxiety disorders.1.- ECG2.- 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 test11.- Body mass Index (BMI)We will be seeking to additionally develop new areas where the analysis methods and datamining approaches we possess offer great promise. For example, In 2000, according to the WorldHealth organization (WHO), at least 171 million people or 2.8% of the population suffered fromdiabetes. The number is increasing rapidly, and by 2030, the number will double. Type 2 diabetesis more common in the Western world, where urbanization and lifestyle changes have increasedthe prevalence of the illness, and an environmental (dietary) affect is implied. Type 2 affects upto 95% of the US diabetes population. 18.6% of those above 60 have diabetes, from the National
  5. 5. Health and Nutrition Examination Survey. In particular, the system we propose specificallypredicts the diabetes variables of a patient for the next scheduled doctor’s visit. Alarming valuesin these predictions can trigger automatic warnings to the medical professional allowing forscheduling more frequent visits, which allows the medical professional to timely intervene. Topredict the future diabetes variables from past data, we propose to use artificial intelligence andmachine learning techniques. Our algorithms will be trained on the existing rich set of patientdata in the Utah diabetes database. Various AI and ML techniques are candidates to be adapted tosuccessfully achieve this goal. One approach would be to view the patient as a dynamicalsystem, 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. Givensuch a dynamics model, it can readily be used to predict the patient’s state into the future, and itis able to provide a measure of (un)certainty about its prediction. Another class of techniquesbuilds on Artificial neural networks (ANN), which is a powerful empirical pattern-recognitionand mapping tool for different data, including approximation of complex nonlinear relationships,as well as different outcomes that characterize individualized epidemiological trajectories. Inpersonalized healthcare, these trajectories are revealed as epigenetic influences accompanied bydiscrete medical indicators. Instead of imposing an a priori model on the data, ANN learns inputand output relationships directly from the data. The flexibility of the ANN models has led tosuccessful application in population pharmacokinetic and pharmacodynamic data analysis.Standard medical information and local clinical studies will be related to one or moreconventional psychiatric scale metrics such as the Hamilton Anxiety Scale, Hamilton DepressionScale, Positive and Negative Syndrome Scale, Clinician-administered PTSD Scale, MississippiScale for Combat-Related PTSD, and Watsons criteria for PTSD in the veteran arms of thestudies. 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 serumassays will be collected to determine the levels of stress markers such as cytokines andchemokines to further verify the results through multiparameter analysis techniques. Lastly, sincethe ECG inherently reflects many aspects of the heart’s physical status, it is possible that in theprocess of mining neurological information from ECG parameters, Innoception may alsouncover new marker patterns for certain cardiovascular conditions. This possibility is considereda secondary facet of the proposed research project, and relevant discoveries in the cardiovascular
  6. 6. areas will be documented for further investigation. It should be observed that A-Fib and otherchronic heart conditions may have a higher incidence in veteran populations than in the generalpopulation. Innoception will develop and employ multiparameter analysis techniques in astructured investigation of complex bio-signal parametric relationships associated with anxietydisorders in the ECG bio-signal. As progress is made in discovering collective ECG parametercorrelations to anxiety traits, additional bio-signal parameters from other bio-signals, such asblood pressure, and skin conductance will be included in the study to develop a multi-modalapproach for objective neurological state analysis. II. CollaboratorsDrs Ed Fila and Regina Drueding (co-founders) have been pioneers and successful entrepreneurs in CVDprevention and CIMT development. They, in prior entities, developed the CIMT software that receivedFDA approval, sold to an ultrasound manufacturer, and established several CIMT outsourcing companiesthat today are the primary industry players. Dr. Fila has also been intimately involved in researchingcancer prevention (including researching facilities or practitioners getting exceptional results), treatingdepression, 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 theeffort to establish cardiovascular measurement with this technology. Two other founders contributeengineering, QC, project management, IT systems, marketing and business skills.Tomasz Petelenz PhD and Robert Tuckett PhD will guide the bioengineering aspects of the project, bothwith extensive experience in the assessment and measurement of relevant physiological parameters thatrelate to health and wellness.Proprietary technologies that will be utilized include biochemical analysis of the breath, developed byRoyce Johnson PhD, and the use of blood markers to quantize the neurological level offunctioning/injury developed by Banyan Pharma. We feature the combination of these new technologiesthat we consider critical to the capture of a meaningful and accurate dynamic measurement ofphysiological baseline and will actively collaborate with them in utilizing these proprietary technologieson the Innoception platform.Breath analysis for health diagnosis and management: The principle long-term target for EZKnowz™ isfor 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 arenot adequate. In search of fresh approaches, it worth noting that the computer technology industry isone of the few industries where the cost becomes lower year after year, driven by Moore’s Law, where
  7. 7. computer power doubles every 18 months. Creative coupling of this digital power offers a chance to reinin the spiraling cost of healthcare. The question is: What is the optimal way of implementation ofcomputing 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 andmoney is spent on patients visiting their doctors or a clinic and too little attention is afforded topreventive care”. Improvements in preventive diagnostics will help reduce hospital admission costs andallow 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 monitorthe health status of individuals in a home environment in real time. These diagnostic devices should beable to digitize the collected information and use the internet to transfer data and communicate with thedoctor’s offices. Powerful consumer gadgets already exist that are simple to use and consistent with theexisting PCs infrastructure, whether this is smart phone, IPad, a notebook, etc. Our vision is to emulatethe IT/PC revolution by empowering the individuals with digital, personal, real time monitoring devicesfor the purpose of preventive care and facilitating early diagnostics. why we cannot communicate withdoctors without face to face meetings, and there is no reason that preventive care should not haveexcellent remote medical coverage. We and many others believe that there is a huge businessopportunity here!For example, one study has identified as many as 3,481 components in human breath. Alreadycorrelations between increases in specific components (markers) with physiological sources andconditions 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 ofbiochemical markers that have been investigated in TBI, our discussion will include the mostcurrent and widely studied ones. The most extensively studied among these are glial protein S-
  8. 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 withdegree of injury; conflicting results exist (3-11). S100β is the major low affinity calcium bindingprotein in astrocytes (3) and it is considered a marker of astrocyte injury or death. It can also befound in non-neural cells such as adipocytes, chondrocytes, and melanoma cells (12). Elevatedserum levels have been associated with increased incidence of post concussive syndrome andimpaired cognition (13,14). Other studies have reported that serum levels of S-100β areassociated with MRI abnormalities and with neuropsychological examination disturbances aftermild TBI (15,16). A number of studies have found significant correlations between elevatedserum levels of S-100β and CT abnormalities (17-19). It has been suggested that adding themeasurement of S-100B concentration to clinical decision tools for mild TBI patients couldpotentially reduce the number of CT scans by 30%.84 Other investigators have failed to detectassociations between S-100β with CT abnormalities (3,20-22). The vast majority of these clinicalstudies have employed ELISA to measure levels of S100B. Although S-100β continues to beactively investigated and remains promising as an adjunctive marker, its utility as a biochemicaldiagnostic remains controversial. Some studies have observed high serum S-100β levels intrauma patients without head injuries suggesting that it lacks CNS specificity and is releasedfrom peripheral tissues (23-25).Neuron specific enolase is one of the five isozymes of the gycolytic enzyme enolase found incentral and peripheral neurons and it has been shown be elevated following cell injury (26). Ithas a molecular weight of 78 kDa and a biological half-life of 48 hours (27). This protein ispassively released into the extracellular space only under pathological conditions during celldestruction.Most studies employed an enzyme immunoassay for NSE detection. Many of these studies eithercontained inadequate control groups or concluded that serum NSE had limited utility as a markerof neuronal damage. Early levels of NSE and MBP concentrations have been correlated withoutcome in children, particularly those under 4 years of age(1,2,28,29). A limitation of NSE isthe 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 ofCNS injury. Tau is preferentially localized in the axon and tau lesions are apparently related toaxonal disruption (31,32). CSF levels of c-tau were significantly elevated in TBI patients
  9. 9. compared to control patients and these levels correlated with clinical outcome (33,34). Thoughlevels of c-tau were also elevated in plasma from patients with severe TBI, there was nocorrelation between plasma levels and clinical outcome. A major limitation of all of thesebiomarkers 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 asignificant relationship with severity of injury and clinical outcome (35-40). Following a TBI theaxonally enriched cytoskeletal protein -II-spectrin is proteolyzed by calpain and caspase-3 tosignature breakdown products (SBDPs). Calpain and caspase-3 mediated SBDP levels in CSFhave 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). Apromising candidate biomarker for TBI currently under investigation is Ubiquitin CterminalHydrolase-L1 (UCH-L1). UCH-L1 was previously used as a histological marker for neurons dueto its high abundance and specific expression in neurons (41). This protein is involved in theaddition and removal of ubiquitin from proteins that are destined for metabolism (42). It has animportant role in the removal of excessive, oxidized or misfolded proteins during both normaland pathological conditions in neurons (43). In initial studies, UCH-L1 was identified as aprotein with a two-fold increase in abundance in the injured cortex 48 hours after controlledcortical impact in a rat model of TBI (44). Subsequently, aUCH-L1 sandwich enzyme-linked immunosorbent assay quantitatively showed that CSF andserum UCH-L1 levels in rats were significantly elevated as early as 2 hours following bothtraumatic and ischemic injury (45). Clinical studies in humans with severe TBI confirmed, usingELISA analysis, that the UCH-L1 protein was significantly elevated in human CSF44 (46), andwas 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 CSFand 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 MMTBIpatients from uninjured and non-head injured trauma controls and were also able to distinguishmild TBI (concussion patients) from these controls. Most notable was that levels weresignificantly higher in those with intracranial lesions on CT than those without lesions. Glial
  10. 10. Fibrillary Acidic Protein (GFAP) is a monomeric intermediate protein found in astroglialskeleton that was first isolated by Eng et al. in 1971. GFAP is found in white and gray brainmatter and is strongly upregulated during astrogliosis. Current evidence indicates that serumGFAP might be a useful marker for various types of brain damage from neurodegenerativedisorders (47,48) and stroke to severe traumatic brain injury (49-53).Clinical researchers have developed methodological standards for developing clinical decisiontools in order to ensure the validity of study results (54,55). As TBI biomarker researchtransitions from the bench to the bedside there are a number of important methodological issuesthat researchers will have to consider as they design their clinical protocols. Since TBIbiomarkers are being designed for clinical management, the outcome or diagnosis beingexamined will need to be clearly defined and clinically important. In order to ensure externalvalidity and the generalizability of the results, study patients will have to be selected without biasand represent a wide spectrum of clinical and demographic characteristics. When interpreting thedata, clinical variables that potentially affect outcome will require careful consideration in theanalysis. Biochemical markers could help with clinical decision making by elucidating injuryseverity, injury mechanism(s), and monitoring progression of injury. Temporal profiles ofchanges in biomarkers could guide timing of diagnosis and treatment. Biomarkers could have arole in management decisions regarding patients at high risk of repeated injury. Accurateidentification of these patients could facilitate development of guidelines for return to duty, workor sports activities and also provide opportunities for counseling of patients suffering from thesedeficits. Repeated mild TBI occurring within a short period (i.e. hours, days, or weeks) can becatastrophic or fatal, a phenomenon termed ‘second impact syndrome.’Acute CT or MRI abnormalities are not usually found after these injuries, but levels of someneurotransmitters remain elevated, and a hypermetabolic state may persist in the brain for severaldays after the initial injury.Biomarkers could serve as prognostic indicators by providing information for patients and theirfamilies about the expected course of recovery. It opens the door to the initiation of earlytherapies. Identifying at-risk patients with less apparent TBI or differentiating injury pathology inthose with more severe intracranial processes would be tremendously valuable in themanagement of these patients. For example, in a patient with a normal CT scan or MRI, a
  11. 11. biomarker that could predict worsening neurological status or long-term disability would havegreat clinical utility.There have been a large number of clinical trials studying potential therapies for traumatic braininjury (TBI) that have resulted in negative findings. Biomarkers measurable in blood would haveimportant applications in clinical research of these injuries. Biomarkers could provide clinicaltrial outcome measures that are cost-effective and more readily available than conventionalneurological assessments, thereby significantly reducing the risks and costs of human clinicaltrials. Biomarkers that represent highly sensitive and specific indicators of disease pathwayshave been used as substitutes for outcomes in clinical trials when evidence indicates that theypredict clinical risk or benefit.Lack of quickly accessible pathophysiologic information during the post-injury course has madepharmacologic intervention problematic. Biomarkers could provide more timely information ondisease progression and the effects of interventions such as drugs and surgery. Biomarkermeasurements could potentially relate the effects of interventions on molecular and cellularpathways to clinical responses. In doing so, biomarkers would provide an avenue for researchersand clinicians to gain a mechanistic understanding of the differences in clinical response thatmay be influenced by uncontrolled variables.Intoxicated, unconscious, sedated, or polytraumatized patients suspected of having a TBI pose aparticular challenge to emergency and trauma physicians. Biomarkers could expedite theevaluation of such patients by providing information on the degree of brain injury prior toneuroimaging. Biomarkers in this setting could also help determine the need for earlyneurosurgical consultation or transfer to facilities with neurosurgical capabilities. There arepotential military applications as well. Serum biomarkers could help diagnose and/or triage braininjured military servicemen and women. TBI is a leading cause of combat casualty with anestimated 15-20% of all injuries sustained in 20th century conflicts being to the head (57-58).Americas armed forces are sustaining attacks by rocket-propelled grenades, improvisedexplosive devices, and land mines almost daily in the recent conflicts in Iraq andAfghanistan.145 It has been suggested that over 50% of injuries sustained in combat are theresult of such explosive munitions including bombs, grenades, land mines, missiles, andmortar/artillery shells. Neuroimaging techniques to diagnose brain injury acutely and othermonitoring tools that assess secondary insults are not immediately available in combat zones and
  12. 12. such casualties have to be evacuated. Triage and management of brain injured soldiers could besignificantly improved if first responders had a quick and simple means of objectively assessingseverity of brain injury and ofmonitoring secondary insults.There is a unique opportunity to use the insight offered by biochemical markers to shed light onthe complexities of the injury process. Accordingly, certain markers could be used as indicatorsof damage to a particular cell type or cellular process or may be indicative of a particular type ofinjury. Neuroanatomically, that could include evidence of, say, primary axonal damage versusglial damage. With such heterogeneity the solution may not lie with a single biomarker but morewith a complementary panel of markers that may prove useful in distinguishing differentpathoanatomic processes of injury. III. Development of Healthbooks™In the business model using software as a service (SaaS), users are provided access to applicationsoftware and databases. The cloud providers manage the infrastructure and platforms on which theapplications 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. 13. mobile app while the business software and users data are stored on servers at a remote location.Proponents claim that cloud computing allows enterprises to get their applications up and runningfaster, with improved manageability and less maintenance, and enables IT to more rapidly adjustresources 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 asguests. Pools of hypervisors within the cloud operational support-system can support large numbers ofvirtual machines and the ability to scale services up and down according to customers varyingrequirements.) 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 areanetworks (VLANs), and software bundles. IaaS-cloud providers supply these resources on-demand fromtheir large pools installed in data centers. For wide-area connectivity, customers can use either theInternet or carrier clouds (dedicated virtual private networks).
  14. 14. Cloud computing relies on sharing of resources to achieve coherence and economies of scale similar to autility (like the electricity grid) over a network. At the foundation of cloud computing is the broaderconcept of converged infrastructure and shared services.The underlying concept of cloud computing dates back to the 1950s, when large-scale mainframebecame available in academia and corporations, accessible via thin clients / terminal computers. To makemore efficient use of costly mainframes, a practice evolved that allowed multiple users to share both thephysical access to the computer from multiple terminals as well as to share the CPU time. Thiseliminated 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-pointdata circuits, began offering virtual private network (VPN) services with comparable quality of servicebut at a much lower cost. By switching traffic to balance utilization as they saw fit, they were able toutilize their overall network bandwidth more effectively. The cloud symbol was used to denote thedemarcation point between that which was the responsibility of the provider and that which was theresponsibility of the users. Cloud computing extends this boundary to cover servers as well as thenetwork infrastructure. As computers became more prevalent, scientists and technologists exploredways to make large-scale computing power available to more users through time sharing, experimentingwith algorithms to provide the optimal use of the infrastructure, platform and applications withprioritized 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 achallenge in that the value of information (VOI) becomes a key consideration- allowing themeaning of medical data to the patient will be considered a HIPAA violation in the furue. Todaywe rely heavily on digital data streams to analyze everything from the timing microwave ovensto 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 shortsound. maybe even some rhythm Some very adept in Morse code could understand the variousclicks as a language. Digital data would not be very practical without a computer. - imaginereading this document in Morse code! Fortunately, modern fast computers exist to eliminate thatboredom..
  15. 15. Lets look at our objective: Provide a improved quality of life through a few simple, unobtrusivedevices 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 areflying North and you have a cross wind to the West it is obvious – to correct - one needs to fly alittle bit East. The key is a constant data stream that is routinely interpreted for all aspects ofhealth – those that are bad, those that are good and all those in between. Collected data is thennormalized for each individual that can be compared to the general populace instead of the otherway around. Once a data stream is collected it can then be easily transformed to be easilyunderstood much like this document had be transformed from Morse code. HIPAA compliancerequires that the architecture of the system be designed for failure- not just the interruption of thedata-architecture but the loss of connections that are essential to preserve the meaning of thedata.Failure to decouple the links between the applications and the sources of data, especially whenthey are likely to be so numerous, would be catastrophic. Applications must not be designed toexpect data, especially transient data, but the application and the device must be expected tointercommunicate—but to execute completely independent of each other. A last example to
  16. 16. consider is the accelerating pace of business itself. Back-office systems have been designed andbuilt for years to run with extremely high performance and throughput. These back-officesystems have been measured by transactions per second, and response times to the submission ofan individual piece of work. As teams move to accessing and even running these solutionsoutside the enterprise, they continue to expect the reliability and the speed of response seenwithin the enter-prise domain. To try to achieve this will require substantial evaluation of how toimplement this connectivity to try to balance these requests. When it comes to responding torequests, 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, butin fact can be used to describe the more-dynamic allocation and use of in-house IT resources, orcloud 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. Businessleaders 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 thismight be for cost-saving reasons, or it might be for more flexible deployment in response to agrowth in usage, or it might simply be the fastest way to get something done. Whatever thereason, 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 looselyconnected, but reliably and securely connected, enabling business teams to make decisions ondeployment completely independent of the application architecture itself.Applications and the business IT infrastructure itself needs to be robust enough, and mustperform fast enough, to consume and take action on all the data and all the events, in a timelymanner. Other data can be held and processed to extract the remaining value. Indeed, theapplications and infrastructure must be both high-performing and “smart.” Applications andinfrastructure must not only be able to recognize the data that was previously important, but mustchange to be able to identify and act upon some of the rest of the Big Data, creating the newbusiness opportunities that Big Data represents, even while Big Data creates new challenges tothe 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 enterprisemessaging. This is a similar approach to the embedded JMS messaging mentioned above, but avoids the
  17. 17. limitations of being Java only, and of only connecting to other instances running in the same applicationserver 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 andtransactional integrity. And although it is different from a file transfer solution, enterprise messaging canbe used to enhance, replace or update an existing or a new file transfer-based approach withoutapplication 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 apart of the programming model. Using JMS is therefore a natural way for such applications to move datainto 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 applicationand the receiving application are running a common JMS provider. Although JMS is a standard API, thewire format is not standard, so different JMS providers cannot exchange messages IV. Our corporate advantages for the researcher include:
  18. 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. Serumneuron-specific enolase, S100B, and myelin basic protein concentrations afterinflicted and noninflicted traumatic brain injury in children. J Neurosurg. Jul2005;103(1 Suppl):61-68.[2] Berger RP, Beers SR, Richichi R, Wiesman D, Adelson PD. Serum biomarkerconcentrations 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 inpaediatric TBI. Pediatr Neurosurg. 2007;43(4):258-264.[4] Martens P. Serum neuron-specific enolase as a prognostic marker for irreversible brain
  19. 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 severetraumatic 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 arepoor 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 andneuropsychological 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 ofpatients 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 CerebrovascularDiseases. 1998;7(4 (July-August)):234-241.[11] Roine ea. Neurological outcome after out-of-hospital cardiac arrest. Prediction bycerebrospinal 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 withincreased 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 earlymagnetic resonance imaging after minor head injury. Case report. J Neurosurg. Nov1996;85(5):945-948.[16] Ingebrigtsen T, Waterloo K, Jacobsen EA, Langbakk B, Romner B. Traumatic braindamage in minor head injury: relation of serum S-100 protein measurements tomagnetic resonance imaging and neurobehavioral outcome. Neurosurgery. Sep
  20. 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-100protein 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 computedtomography 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 providesadditional information fot the indication of computed tomography in patients afterminor 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 ofserum creatine kinase BB as index of brain damage after head injury. Br Med J. Sep20 1980;281(6243):777-779.[21] Rothoerl RD, Woertgen C, Holzschuh M, Metz C, Brawanski A. S-100 serum levels afterminor 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 S100Blevels and intracranial injury in children with closed head trauma. Pediatrics. Oct2009;124(4):e697-704.[23] Rothoerl RD, Woertgen C. High serum S100B levels for trauma patients without headinjuries. Neurosurgery. Dec 2001;49(6):1490-1491; author reply 1492-1493.[24] Romner B, Ingebrigtsen T. High serum S100B levels for trauma patients without headinjuries. Neurosurgery. Dec 2001;49(6):1490; author reply 1492-1493.[25] Anderson RE, Hansson LO, Nilsson O, Dijlai-Merzoug R, Settergen G. High serumS100B 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 kinaseBB and neuron specific enolase following head injury indicates brain damage. ActaNeurochir (Wien). 1992;115(3-4):106-111.[27] Schmechel D, Marangos PJ, Brightman M. Neurone-specific enolase is a molecularmarker for peripheral and central neuroendocrine cells. Nature. Dec 21-281978;276(5690):834-836.[28] Varma S, Janesko KL, Wisniewski SR, et al. F2-isoprostane and neuron-specific enolase
  21. 21. in cerebrospinal fluid after severe traumatic brain injury in infants and children. JNeurotrauma. Aug 2003;20(8):781-786.[29] Bandyopadhyay S, Hennes H, Gorelick MH, Wells RG, Walsh-Kelly CM. Serumneuron-specific enolase as a predictor of short-term outcome in children withclosed 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 plasmaduring and immediately after extracorporeal circulation. Ann Thorac Surg. Mar2000;69(3):750-754.[31] Kosik KS, Finch EA. MAP2 and tau segregate into dendritic and axonal domains afterthe elaboration of morphologically distinct neurites: an immunocytochemical studyof cultured rat cerebrum. J Neurosci. Oct 1987;7(10):3142-3153.[32] Higuchi M, Lee VM, Trojanowski JQ. Tau and axonopathy in neurodegenerativedisorders. Neuromolecular Med. 2002;2(2):131-150.[33] Shaw GJ, Jauch EC, Zemlan FP. Serum cleaved tau protein levels and clinical outcomein 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 insevere brain injured patients: association with elevated intracranial pressure andclinical outcome. Brain Res. Aug 23 2002;947(1):131-139.[35] Cardali S, Maugeri R. Detection of alphaII-spectrin and breakdown products inhumans 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 AndBreakdown 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 SpectrinBreakdown 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 inHuman CSF and Outcome After Severe Traumatic Brain Injury [abstract]. AcadEmerg Med. May 2005;12(5 (Suppl 1)).[39] Farkas O, Polgar B, Szekeres-Bartho J, Doczi T, Povlishock JT, Buki A. Spectrinbreakdown products in the cerebrospinal fluid in severe head injury--preliminary
  22. 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. JNeurotrauma. Jul 2010;27(7):1203-1213.[41] Jackson P, Thompson RJ. The demonstration of new human brain-specific proteins byhigh-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 interactionbetween ubiquitin-conjugating enzymes and the 26S proteasome. Mol Cell Biol. Jul2000;20(13):4691-4698.[43] Gong B, Leznik E. The role of ubiquitin C-terminal hydrolase L1 in neurodegenerativedisorders. Drug News Perspect. Jul-Aug 2007;20(6):365-370.[44] Kobeissy FH, Ottens AK, Zhang Z, et al. Novel differential neuroproteomics analysis oftraumatic 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 biomarkerfor 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 markersfor 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 fibrillaryacidic protein and S-100B in hippocampus and cortex of diabetic rats: effects ofvitamin 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 fibrillaryacidic protein within degenerating astrocytes of the Alzheimers disease brain. Am JPathol. Mar 2006;168(3):936-946.[49] Missler U, Wiesmann M, Wittmann G, Magerkurth O, Hagenstrom H. Measurement ofglial fibrillary acidic protein in human blood: analytical method and preliminaryclinical results. Clin Chem. Jan 1999;45(1):138-141.[50] Pelinka LE, Kroepfl A, Leixnering M, Buchinger W, Raabe A, Redl H. GFAP versusS100B in serum after traumatic brain injury: relationship to brain damage andoutcome. J Neurotrauma. Nov 2004;21(11):1553-1561.
  23. 23. [51] Pelinka LE, Kroepfl A, Schmidhammer R, et al. Glial fibrillary acidic protein in serumafter 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. Measurementof glial fibrillary acidic protein in blood: an analytical method. Clin Chim Acta. Dec2002;326(1-2):151-154.[53] Nylen K, Ost M, Csajbok LZ, et al. Increased serum-GFAP in patients with severetraumatic 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 decisionrules 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 suggestedmodifications of methodological standards. Jama. Feb 12 1997;277(6):488-494.[56] Carey ME. Analysis of wounds incurred by U.S. Army Seventh Corps personneltreated in Corps hospitals during Operation Desert Storm, February 20 to March10, 1991. J Trauma. Mar 1996;40(3 Suppl):S165-169.Proteomics – Human Diseases and Protein Functions106[57] Sapsford W. Penetrating brain injury in military conflict: does it merit more research? JR Army Med Corps. Mar 2003;149(1):5-14.[58] Okie S. Traumatic brain injury in the war zone. N Engl J Med. May 192005;352(20):2043-2047.Addendum: Common correlation with physiological symptoms and disease states. Pain Fatigue Mood Digest SleepUnderhydration P P P PFood sensitivities P P P P PJoint subluxations P PRadiculopathies P PMyelopathy P P P P PViscerosomatic reflex PInfectious malaise P P PArthritides P
  24. 24. Low bone densitiy P PHypovitaminosis D P P P PCalcium deficiency P P P PIron deficiency P PMagnesium deficiency P P PTyrosine deficiciency P P P PFatty acid deficiency P PZinc deficiency PHypoadrenia P P P PHyperadrenia P P P PAAT deficiency P PPoor posture P PParasite infection P P P PNon-restorative sleep P P PMetal toxicity P PCandidiasis P P PDysbiosis PDysglycemia P P PHyponatremia P PAnemia PHypothyroid P P P PFunctional acidosis P PForeign energies PZeta virus PPancreatic insufficiency PH. pylori infection PHypochlorhydria PProlapsed colon PHiatal hernia PRib torque PMedication side-effects P P PRetless legs PMeridian dysfunction PLight & sound dysruption PPoor stress management P P P P P