2009-11-24

The Overblown Cytokine Storm and 225G from 1918

225G is not new and this "Cytokine Storm" phraseology is overblown.

The public perception of 225G and the media linkage to hemorrhagic pneumonia is new. 

These Hydra Effect viral backgrounds carrying 225G within ΣPF11 are, in fact, very dangerous strains for what they are doing now and, more importantly, for where they are going . . . no question exists about that risk tendency.  The only question is why hasn't the science community driven the clinical linkages to the forefront before this week?  Fatal outcomes have been documented on record since July in multiple cases from Brasil.

Obverse speculation is also dangerous, especially risky when speculating based on poorly defined terms.  Banter and rant occur with much vitriol and then everyone who needs the data stops listening.  Few conversations are more demoralising that the ones where you have no anchor point on the major terms.

A primary topic of concern is Cytokinic Dysregulation.  Reliance on inspecific phrases like "Cytokine Storm" in the media will only continue to misinform the public on a process that is far less understood than the lead investigators would like to admit.

All of which returns us to the basic categories:
  • What we do know?
  • What we don't know?
What we do know?

Now that 225G matched clinical data is available, however limited, a potential correlation is being drawn on lung tropism. The standing bench studies, including the Palese and JKT team collaboration in 2006, detailing variant tropism based on differential HA reception at α2-3 and α2-6-linked sialic acids evaluated correlative to aa225 lend evidence to the concept of deep lung involvement though the experiments were conducted by varying permutations of aa190 and aa225 on 1918 variants.  Whereas, we stand in 2009 with quite different genetics that require cross-validation prior to citation with applicability to PF11.

Tissue type targets are compelling studies and this particular superarray protocol may prove even more useful on PF11 than 1918 samples.  We note that though 1918 and PF11 now share 190D and 225G, that all 1918 public sequences show 206S206T continues to emerge and conserve regionally in PF11.  All 225G bearing strains after April show 206T, except the July CatNS1706 and the undated Vladivostok01.

Reproducing the glycan microarray procedure with the contemporary and ideal dataset including Brasil and Catalonia may bring a tigher focus onto today's issues.  We couldn't ask for a more balanced set of control factors with Catalonia offering sequences less than one week apart demonstrating both important pairings: 206S/225G and 206T/225G . . . a bench review made to order.

We also do know that a proper immune response, that is a timely and regulated innate immune response, is not occurring in certain of these patients. When the n +1 generations of the virus progeny begin to lyse the host cells, that failure of innate immune function to have responded early leads to an undetected and massive viral load due to the rapid replication trait of PF11. The cell detritus and the density of moving viral particles elicit a host-driven, limited “self-destruct” series of events because the multiple levels of early detection parameters have been bypassed leaving the core essentially defenseless.

What we don’t know?

Much of what we need to know today about Cytokinic Regulation is yet to be studied. 

The systems of feedback loops are extensive with individual effectors often having multiple functions, in some cases, opposing functions.  So please bear in mind that we are looking into an instantaneously self-modifying system that not only self-revises the systemic parameters, but recruits and removes players in the middle of the game and then encourages them to change sides without even changing jerseys.  And to top the difficulties, Heisenberg applies.  Tighten down the screws to look at one molecule and his best friend will no longer stand anywhere near him, though they were conversing with verve before we attempted to measure.

That disclaimer in place, you may still note important aspects of proper cell-to-cell signaling systems from the following discussion as you keep in mind that the presentation is highly compressed for educational purposes.

Though Cytokinic Dysregulation is occurring in most PF11 cases at some level of interchange, the 225G and 225E strains may potentially interfere at a more profound level with the early innate response by amplifying the PF11 conserved effect of the NS1 paired Glutamates at aa96 & 97 that constrains the IFN synthesis instantiation cycle by binding TRIM25, an early catalyst to RIG-I ubiquination.  Influenza bench researchers don’t know exactly where the failure is occurring or at which combination of cell-to-cell signalers in PF11 or the PF11 225G strains.  Until those identification studies are designed, undertaken and reproduced, discussion at this point is stark hypothesis based frequently on the speaker’s sheer lack of present research content mastery. Apparently, saying “I don’t know?” and then returning to the bench to design and gather a proper foundation of data is a skill rarely encouraged in our “Science for Hire” era.

Our team is unimpressed that the wider science community, with such broad analytical skills and exceptional equipment, relies on pseudo-explanation, this cloud of diversion, by invoking the “Cytokine Storm” phrase.  More than 20 well-characterised and 100 identified distinct molecular signal functions are at work in the early immune response, including cytokines, but not limited to that class of communicators.  Tagging a term for PR purposes is much simpler than tagging a molecule for tracking, but you received your instruments because you can think, not for your ability to improvise inventive talk.

Think.

Eighty billion dollars in research should arrive at a better answer with higher specificity and actionability than the blanket “Cytokine Storm” tome.  Data and procedure discover Facts.  Anything less is purely Public Relations.

Our team continues to hold an opinion that we first described in 2006 concerning Cytokinic Dysregulation and the NS1 protein of Influenza.  Succinctly, the viral ability to suspend innate immunity for up to two days post-infection, as characterised by Mount Sinai this year, prevents the early and required pro-inflammatory Cytokinic Response to viral detection.  That blunting, taken in conjunction with detailed studies around adaptive immunity, may result not only in failure to clear the virus from some patients in a timely fashion, but also in failure to produce a useful quantity and competence of memory T-cells and Ab.  The early failure to clear a rapidly replicating virus like H5N1 or PF11 results in a frank trauma to the immune system when the first generations of viral progeny lyse their host cells after being undetected and flood the tissues with virii and toxic cell detritus.  That disorderly surge of human and viral proteins en masse activates a late and cascading pro-inflammatory response that frequently fails to down-regulate properly.

This explanation is contrary to "pop" science reports that a normal and robust immune response over-generates cytokines and attacks self indiscriminately.  We hold that, by the time the virus has lysed thousands of cells and released millions of virii, that most adjacent tissue areas are "fair game" for immune response due to toxic cell detritus and viral travel.  That flooding of antigen and waste matter, widespread and instantaneous to the immune system, may further interact with some virally induced derangement of the alternative pathway of complement and generate the intensive up-regulation of signaling, pro-inflammation cascades and the resultant tissue damage described in the clinicals as DIC, DAH and ARDS.

Ergo, the findings of massive tissue damage on necropsy is the result of a failed early innate immune response, not a normal robust response.  A normal, properly up- and down-regulated robust innate response clears infection in more than 90% of various infections (viral, fungal and bacterial) and proceeds to generate Ab in short order via the adaptive arm of immunity.

When viral hosting cells properly detect intrusion, flag themselves for apoptosis (cell death) and are then assisted by cytotoxic T-cells, the injection of fragmentins via perforin "tubes" induces an endogenous apoptotic program literally cutting DNA into 200 base multimers (fragments) and eventually condensing chromatin.  That organised molecular result is far less inflammatory and far more useful for antigen identification than the disorderly outcome of a virally "exploded" cell.  Now you can see why proper genetic expression during each phase of this programmed cell death guarantees a lower pathology than the chaotic and toxic outcome of lytic host cell destruction resulting from viral NS1-induced, delayed genetic expression. 

A confluence of PF11 traits (failed early detection, multi-tropism and rapid replication) against the host-pathogen interface may force a limited "self-destruct" in the host upon eventual detection in an attempt to save the organism.  That limited "self-destruct" is not the desired outcome of a normal and robust immune response, but occurs due to a failure of the immune system to detect and respond early in the process.

Timing matters. 

Individual viral genetics and individual host immune genetic expression are primary effectors that must no longer be discounted under the clouds of some nebulous "Cytokine Storm" or Mysterious Mutation.

Cytokinic Dysregulation is wider than immunity. 

Johns Hopkins School of Public Health estimates that half of all Americans suffer from chronic illness.  150 million in one country.  Cytokinic Dysregulation is a very real situation occurring daily in the lives of a significant group of chronic illness sufferers as a component of asthma, chronic joint damage, digestion tract insult, diabetes, endocrine dysfunction, vascular inflammation of undisclosed cause, detoxification pathway insult (renal/hepatic), immune dysfunction, obesity and numerous sub-clinical, but accumulative pathologies.  Each of these suffering individuals is at an increased PF11 risk based on the types and levels of cell-to-cell signaling failures across their systems.

So let's stop talking about this overblown "Cytokine Storm" and begin candid discussions with specificity about causality.


For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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2009-11-23

Hemorrhagic Pneumonia: CDC Issues Alert to Physicians for Heightened Surveillance

This report is preliminary and will be reviewed for corroboration as the official documents become available.

Although confirmation is not yet complete on this item, the American CDC has apparently issued an alert to physicians concerning hemorrhagic pneumonia in the United States.  The North Carolina Medical Society has published a description of the CDC alert and has identified a reporting point in their state. 

The PF11 viral reservoir is extending and revising in important areas concerning trait enhancements.  Since the early part of the pandemic, this viral reservoir has exhibited exceptional abilities to damage the human body due to Influenza Flux; however, we may now be moving into deeper water if this alert is validated.  While no one may say exactly where this virus is going, we are able to track the genetics and the human clinical outcomes correlated to those genetics.

Deep lung involvement appears to be supported as a trait enhancement via the D225G polymorphism on the viral Hemagglutinin.  225G is not a new incursion into ΣPF11, but now paired with 206T is becoming a higher concern.  The US and Mexico demonstrated 225G with 206S early in the pandemic.  206T, as predicted, has now become fixed or consensus in many geographies.  Recent studies on the Ukraine, Russia, China and Norway show 225G in the Hemagglutinin to be circulating alongside the dangerous 225E and the wildtype 225D bearing strains.

Heightened surveillance is being required from the medical community while the general public is receiving communications with an alternate message?  Moms and Dads will want to get ahead of this issue by gathering accurate and complete information as soon as possible.  PF11 will be with us for a long time.

Gather and Solve.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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2009-11-22

TamiFlu Resistant Cluster of 4 at Duke Medical Center, North Carolina, US

As the thirteenth TamiFlu Resistant sequence was released publicly by Italy demonstrating a hypermorphic progression to another novel strain, the Duke University Medical Center contemporaneously described a group of patients acquiring PF11 Influenza in an isolated ward of their hospitalFour of the patients from this isolated ward were found to be infected with a TamiFlu Resistant strain.  Transmission is suspected and may be verified by publication of all sequences from that ward over a time period covering two weeks prior, during and two weeks after the event.  Three of the four patients had fatal outcomes (75%).

Antiviral resistance has now been documented in 50 instances, when investigated, including North America, Europe and widely across Asian countries.  The 13 sequences that are available are, for the most part, incomplete for research into cross-segment linking of Hemagglutinin (HA) polymorphisms correlative to the antiviral-resistance conferring H275Y Neuraminidase (NA).  Investigators are left at bare benches staring into empty beakers waiting for catalyst. 

The resistance marker is now found on numerous backgrounds potentially demonstrating an ability to travel as a silent sub-species.  Up to this current stage of the pandemic virus progression, this resistance trait, in several cases, appears to arise in an individual as the prominent super-infection (co-infecting silent H275Y PF11 strain) based on some unidentified characteristic of the individual's host-pathogen meshing, including immune dysregulation or other existing Cytokinic Dysregulation morbidities.

Publication of the remaining 37 sequences, including the Duke University Medical Center clinicals from this prestigious research institution, may benefit worldwide understanding of the efficacy and longevity of currently promulgated mediation measures for PF11.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

2009-11-06

Ukraine Expected to Surpass 1 Million Infections in Only 10 Days; the U.S. took 10 weeks.

A day in the Ukraine is like a week in the United States . . .

for Pandemic Influenza spread, that is.

On October 29, the Ukraine officially reported an uptick in Influenza-like-Illness (ILI) and a surge in hospitalisation.  Concomitant deaths were reported from hemorrhagic pneumonia and four doctors were soon included in the fatality pool.  The situation was recognised and immediate action was taken.  Very early in the process, a nationwide alert was issued and the situation came under central management.  In mere days, the healthcare infrastructure was stressed and supplies were exhausted.  Resources have been redirected and escalations continue.  Citizens are cutting their own clothing to make masks.

Tomorrow will mark 10 days since that spark. 

Based on the most recent daily case increases trending upward from 32% to 37%, we expect the Ukraine to surpass one million reported infections by Saturday afternoon, November 7, 2009.  If the reporting trend continues with the weekend and the rates hold, just under 1.2 million cases will be cataloged.  We cannot speculate if a report will be made publicly available on Saturday.

The official reports from the United States indicated that 1 million infections were reached in late June 2009, 10 weeks after the initial sparks of PF11 began to ignite the populations and burn through the major cities.

The Ukraine progression defines a new method for PF11.  In the early phases of any catalyst event, all statistics are suspect, but the trending is often useful.  Official numbers, upon some minor calculations, demonstrate that the daily increase in hospitalisation and deaths is rapidly climbing.  Yesterday the increase in daily hospitalisations was 20% and today the increase is 37%, almost a doubling in day-to-day velocity.  Yesterday the increase in deaths was 17% and today the increase is 42%, more than a doubling in day-to-day velocity. 

Data reporting cut-offs are always at issue in these early inflows, but over the next two weeks an exacting pattern will be defined.  Researchers must be given access to the raw data to determine causality and vectoring.  A significant library of samples has been received and sequenced in a prestigious European coordinating laboratory.  No data at this time has been released. 

Timeliness is essential when a virus has marched to 1 million suspect cases in only 10 days in one country of less than 50 million people.  1 of 50 ill across 10 days.  Clinical and environmental data matching the sequences will be critical to deduce and weight the parameters driving this regional escalation.  Those who will writeoff these flashpoints as medical infrastructure failures and sub-standard housing problems endemic to the third world are not intellectual Titans.  A pandemic is by definition unpredictable in phase shift timing and degree.  To discount this Ukrainian surge in suffering to poverty is simply academically irresponsible in a pandemic era.  These data points requested, if made public today, may save the lives of many in the area and exponentially more in the coming months around the globe.

The Ukraine is bordered by the countries of Russia, Belarus, Poland, Slovakia, Hungary, Romania and Moldova.  The southern area of the Ukraine is involved in several bird migration routes being bordered by the Black Sea.  Sequence examination of late summer specimens from these bordering areas and Eastern Europe demonstrates a trend equal to the United States with a significant Hydra Effect and substantial Antigenic Diversity delivered via Influenza Flux.  US sequences certainly match and even advance the polymorphisms in Eastern Europe and these border nations.

Our studies clearly demonstrate a one to three week lag at maximum in transport time and acquistion into new geographic areas of trait-enhancing genetic material within ΣPF11.  The stage is already set with similar sequences existing in most parts of the world.  225E has continued to penetrate in dozens of nations and is a factor in our present working hypothesis for this Ukraine spark. 

If the Ukraine has variant genetic specimens, the information is primary to world health.  Singapore was recently courageous enough to release 600 sequences that widely demonstrate movement in the reservoir.  Only an immediate evaluation of the full dataset of Ukrainian sequences and matched clinical information will provide countries the opportunity to prepare if this incident does mark an inflection point or catalyst event in the pandemic.

Is the US only one cold winter week from the situation today in the Ukraine?  Is the base of Pandemic 2.0 now widening in countries that have some point of susceptability?  If so, the landing strips are presently in place for these new polymorphisms to land on the existing PF11 strains in every basic geographic area of the world. 

We may all be one week from seeing a million new cases in our homelands or, worse yet, watching 2% of our population stricken in only 10 days. You do the math for your nation and then decide if we need data transparency and academic honesty.


For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

2009-10-08

Use Low and Slow Exposure to Make Hungry Antibodies Fast

We produced this article on 2009-05-03 for members of our community in response to questions surrounding the then epidemic which soon became PF11.  The information remains useful as a general guide though the Hydra Effect is more pronounced today.

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As the number of PF11 infections increase within a community, the average newest-exposed or most recently exposed individual in the population will have multiple and, more importantly, persistent viral exposures, significantly more than the individual effect early in the pandemic.

As an epidemic grows, the NEI (Newest Exposed Individual) and their naïve immune system will initially be presented with a substantial particle count from a multitude of variants.  The virus will have made moderate adaptations to the new host, humans, and may, therefore, be more capable due to Influenza Flux.  Many labs have now demonstrated that passage of a novel virus through a new host and / or new host tissue type will lead to selection for host-matching genetics.  Upon this more substantial initial exposure, the NEI’s immune system will naturally have an immediate requirement to mount an innate response and, if successful, to subsequently mature a separate line of antigen-matching B cells for each variant strain of community Influenza (PF11 Hydra Effect).

A separate and important consideration today is that much of the population is immune depleted due to genetic damage and may be missing significant feature functionality in the cell-mediated and humoural responses.  Any heavy taxing may overwhelm the system of the immune-suppressed.

As the boundaries shrink between the non-exposed and the exposed, we may see a higher death rate among the NEI population because their Multiplicity of Exposure and total intake of infective viral particles will be high and variant.

We’ll now examine the idea strictly on a particle count example that is tempered for ease of communication.  These numbers, though simplified, are conservative.

Early in any epidemic, presume that exposed individuals get 1,000 particles to start an infection.  Later individuals will have at least a dozen of their close community who are infected, thus, 12,000 input particles.  Influenza delays and partially disables innate response, so 12,000 input particles is far worse than the small number may seem.  The synergy of 12,000 initial virions attacking a body may have a stultifying effect on immune response, especially on a delayed or late stage immune response. Twelve thousand particles each entering 1,000 on the copy machine within each infected cell may result in twelve million virions circulating freely in one replication cycle, certainly in less than a day. 

Your body is doing a lot of heavy lifting for an unappreciative guest.

Bear in mind that even the early specimens from ΣPF11 have been found to replicate 1,000 times faster in mammals than standard H1N1 Seasonal Influenza, so our very simplified example is vastly underplayed from the reality of what actually occurs in the human body.  Now that the trait-enhancing genetic marker of PB2 E627K has been identified across several geographies in this reservoir, we can expect the additional increase in replication speed to become fixed.

I’m not so sure that anyone’s humoural response can make the required 12 million antibodies for the dozens of genetically variant inputs that will be part of that initial 12,000 particle exposure, at least not in a useful timeframe.  Due to proximity and transport requirements, the NEI may need to make 60 million or more antibodies to accomplish neutralisation of that initial 12 million Influenza variants.  A properly regulated, innate immune response will always be the driving factor in successful clearance of an IDRREAV like PF11.

Then you have the Elimination challenge.  Without an early and powerful macrophage and inflammatory up and down-regulating process, any Cytokinic Dysregulation due to delayed cell-mediated immune response may leave the tissues filled with plasma and the small blood vessels effectively clotted closed, setting off another chemokine cascade to flood the system with anti-clotting agents (DIC).   A well-timed and even response is essential so that elimination may occur on a manageable schedule.

Remember that three phases must be fulfilled sequentially to clear any toxin or pathogen from a biological system.

1. Detect
2. Destruct
3. Eliminate

Failure to operate at maximum potential during any stage means practical failure of the entire system.

Initial exposure reduction may be noted as the most important factor in reducing Influenza severity in a previously healthy host individual.  Slow and Low Exposure protocols ensure that your NEI (n+1) are provided the greatest opportunity for survival and reduced severity.  Communities will fail or succeed in this pandemic based on their Multiplicity of Exposure.  In this pandemic, choices made by each individual may have long-term health implications for that individual and for their community.

How do we establish a Slow and Low Exposure protocol?

In the event of a rapidly replicating Influenza virus, a community’s highest priority must be on social distancing to reduce the number of exposure episodes and the per exposure viral count.  A prominent secondary priority must be to supply the community members with the materials, catalysts and protective time umbrella necessary to make genetically accurate antibodies in a sufficient count to neutralise and defeat those new strains of Influenza.  These two priorities when executed in tandem will create the Low and Slow exposure that allows members of a community to make accurate antibodies fast.

Everyone will eventually be exposed, though not everyone will display outward symptoms.

Each exposed and infected individual becomes a risk at some point to others in the community due to viral shedding.  The initial symptomatic host (index = n) within a community (family, workgroup, school, day care, etc) will be forced to rely almost entirely on innate immune function to overcome a rapidly replicating virus.  A weak innate response puts that individual in the unenviable position of being a rapid viral shedder.  The first exposure in a community is a sentinel to the others.

On the other hand, any subsequently exposed individuals [(n + 1), family members, professional peers, fellow students, et al] may have another route if they are properly managed and supplied.  If the remaining community (n+1) is following hygiene and social distancing protocols to reduce total exposure episodes and viral concentration (per exposure infective particle count), those members may discourage the rabid community burn and promote a Low and Slow Exposure.  Given the additional time due to the lower total infective particle input, the immune systems of the (n+1) individuals may have the opportunity to produce an array of vibrant antibodies before the virus manifests an extensive reproductive cycle and attains the minimum viral count required to produce interior spread and outward host symptoms.

An early and robust innate response to PF11 may be followed by an equally broad antibody build.  That early response, in sufficient numbers, controls the virus in the host and reduces viral shedding, limiting further community illness.  The antibody build, if competent, provides an additional memory function for that individual’s future exposures to genetically matched viral assaults.

Everyone will be exposed.  Work for safety in your community by making your exposure Low and Slow to build hungry antibodies fast.



For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

Can My Child Be Re-Infected If They've Already Suffered from Pandemic Influenza H1N1?

Georgia Mother and Her Children Infected Twice with H1N1

Many cities around the world are reporting re-infections, including US geography in and around Georgia and New York.

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Does an antibody set from a previous infection protect me?  Not always.

Under what conditions do my antibodies protect me?  An antibody response is very protective if timely, in high quantity and matched to the intruding virus.

Viral strains change and PF11 is changing rapidly on the areas that the human body uses for recognition.  If you were trying to identify a villain that you only saw once from the rear, then you’d have to use the clothing as your key. The villain knows that you only saw his clothes and not his face.  Will the criminal change clothes?  Yes.  Will this virus? Yes.

For some reason, people have been led to believe that “getting” PF11 now will be an iron-clad protection from later versions of the disease.  Medical professionals seem to rely on this thinking though their training demonstrates otherwise.  We do have a new Influenza season every year and they do see many patients more than one time in a season.   They do create a new vaccine every year and that vaccine does fail to match or fail to seroconvert much of the time.  They do know that Influenza is variable, but they don’t realise just how variable because they haven’t taken the time to study the ΣPF11 genetic sequences.

We received a response from a friend who is a medical professional noting that her child had been exposed from an extended family member, developed symptoms and appeared to have fully recovered.  We rejoiced that they had been spared significant suffering, but were concerned about the triumphant tone of the message.

Busy people sometimes do not regard the facts well unless the facts fit into their busy schedule.  In fact, busy people sometimes fail to put their own knowledge to work in their own families?  A virus like PF11 does not care about your schedule.

We responded with facts about this particular unprecedented pandemic:

Are you doing anything to ensure that all of you are developing a robust antibody response over the next 21-30 days?  Remember that due to weakened host immune responses a strong percentage of people who are exposed will not seroconvert to a fully protective antibody profile.  Even an individual who does build a basic profile will face future PF11 specimens that have escaped the antibody profiles in that individual host and host family.  That future specimen could occur in less than a month from the initial infection due to the observed PF11 enhanced genetic acquisition trait and the ample circulating diversity in any single geography.  I refer you to the Three Time Loser in 1918.  If the host is traveling, then multiple exposures to variant antigens are ensured.

Maintaining a properly regulated innate immune function is extremely important even after an individual appears to have successfully recovered from the initial exposure cycle.  The antibodies created, if they do seroconvert a protective set, can only be called into action via the initial innate immune response.  The virus must be recognised by the body before any adaptive immune response will be mounted.  A properly regulated innate immune response serves that detection function, acting as a coordinator, determining if matching antibody exists and calling it into action.  Secondarily, a significant count of children and young adults are on file as having appeared to recover and then relapsing to become fatal cases.  This PF11 virus may quiesce the immune system at any phase, early or mid-stream.  The relapse potential is a fact with this viral reservoir.

Influenza Flux between swine, bird and man creates a mismatched host-disease interchange that is highly variable in outcomes.


Succeeding in Round 1 against this virus is great, but now the virus knows that you can block a left jab and will try something new.  As PF11, under the cover of cold weather, learns more about the North American hosts, PF11 will exploit the weaknesses just as the reservoir did in South America in July and August with more than 1,000 deaths in Brasil alone.

Diligence in the Round 2 will determine our success.  You are in a 15 round endurance match.  This virus is well-trained and well-stocked in his corner.  Will we stay on our toes and move one step ahead of the virus or will we rest on our heels leaving our chin exposed for the knockout punch?

Each adult will decide for themselves, but remember that the children are dependent on the adults who head their families and their communities to decide for them.



For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

2009-10-07

US Passes Thousand Death Marker prior to Influenza Season with 1,197 Confirmed Deaths

1,197 Confirmed Pandemic H1N1 Deaths before the Influenza Season begins in the United States and we stopped testing and officially recording most cases in early July, more than 10 weeks ago.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.



Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

2009-09-29

E627K from July Discovered Retrospectively, Tied to Vacation Island off the Netherlands in Diabetic Patient and Adolescent Female

Though the sequences have not been released, the team at Erasmus MC in Rotterdam has done us all a great service by providing an early report of 627K in the Netherlands. 

The multiple cases all vector from visits to a popular vacation island between July 13 and August 9.  Two of the cases do not appear to be related via direct contact, potentially indicating an endemic and silent spread of a minor PF11 population carrying the human-fit virulence factor 627K in a sub-clade that may match the major circulating sub-clade there but for the Lysine recombination.  Ten of twelve (83%) sample specimens from this geography fall into this sub-clade indicating the potential for dominant circulation in that area.

As this release of information via Promed is very limited, additional evalution and insight will require amendment and revision to this article as the matter is clarified on several accounts, including specification of the E627K sequence count and the various ratios confirming the certain Hydra Effect demonstrated in the study population.

In our reading, 4 distinct cases are discussed in the Osterhaus release. Which two of the four are described as having the E627K is questionable and will determine the H2H transmission assumptions.  The researchers may have mentioned “two patients” because the family contact and the younger sister may have been directly evaluated by them in a clinical setting?

  • Male Diabetic who may have shared activities with ill female camper, onset 2009-08-09
  • Female camper, onset after returning home 2009-07-20 
  • Female family contact of ill camper, onset after camper returned on 2009-07-20
  • Younger sister of female family contact, onset 2009-07-23

This highly interpretive post is preliminary based on inconclusive language in the press release.
No mention is made of the correlating PB2 virulence of aa701N and aa703K at this time in the information released.  We suspect these to be absent due to the non-fatal clinical outcomes; however, confirmation would be useful.

As the samples were examined retrospectively, little new observational evidence will be forthcoming.  Rational projections due to this 627K mid-Summer emergence in the Netherlands and the late May emergence in Shanghai71T could cause us to expect a geographically-dispersed, wild-type sub-population carrying this virulence factor.

Tenacious sub-clonal evaluation of current sequences in the United States will likely indicate mixed peaks at the PB2 residue coding for the Lysine at 627.



For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com

2009-09-25

How Long Will the Pandemic Last?

The Road to Post-Omega PF11

How long will the Pandemic last?

Process: Predictions involving the outcomes of unprecedented or entirely new events must utilise theory.  Very few outside the scientific community revel in the joys of Theory, but today you may come to appreciate the practical value of theoretical reasoning.  Theory, the primary tool to explore anything unknown, generally begins with new tags or agreed definitions so that the discussion may embark.  The present framework of discussion, of theory, around PF11 appears to be lacking several important terms, specificity, control variables, causality determination and scientific rigour. 

So let's make an attempt to plant some markers and comport a discussion on one simple and important area of measurement, PF11 Timing.  Let's call today's virus, PF11β, and a future tipping point, PF11Ω, for ease of discussion.  Let's agree that we must progress beyond that future event of PF11Ω before the Pandemic will dissipate.  (Glossary)

The distance between PF11β and PF11Ω is unknown.

And that delta, that difference, will remain unknown until some point in the distant future when we can retrospectively measure the closing event. Today, we'll talk about the road that everyone will travel from this moment until that closing event.

The journey between the two points will be progressively inundated with higher levels of impediment to the traveler. The traveler may not declare an optional routing. Due to decisions made by others, the traveler’s only available option is to agree and undertake the journey as given.

We all are driving the only highway (ΣPF11) between this small town of Bad (PF11β) and the metropolis of Worst (PF11Ω).  We know that no one knows the rate of speed we are traveling because no speedometer may be calibrated for a non-uniform progression.  Measurement is incomplete for all practical purposes. Fits and starts will be the norm.  We also know that each family will be affected by various types of collisions along the way.  In the veritable infinity of infectious vectors, few will emerge without themselves, their family or some important person in their lives being impacted.  Density, proximity and movement guarantee collision in any bounded system and this system is distinctly bounded.

As the traveler succeeds in passing each mile with the almost certain collisions and if they are able to survive the increasing number of attack vehicles (recombinants from the Influenza Flux), the lost segments of road (poorly chosen mediation measures) and the dwindling availability of fueling stations, eventually they will arrive at a better place. Though PF11, this first city on the other side of Worst, is not the ultimate destination, any relief after that pandemic journey will be appreciated and any glimmer of light will be a sight for sore eyes.

Eventual arrival is the key concept. How long will this journey last and what must you do to eventually arrive are the important questions.

Someday long hence, you may rate this trip as “Somewhat Unpleasant” or “Utterly Devastating” depending on how well you’ve equipped your individual journey with actionable Knowledge and viable provisions. Though a fully intact arrival might be your goal, the most capable and well-Led travelers will realise that completion of this journey with only minor impact is a deep blessing because you’re going to need to see around corners to get there at all. While others planned your route straight through renegade territory, the responsibility now falls on you to cross this expanse of impediments and the ostensible rest areas are unprotected.

Renegades abide no law and a virus abides no social messaging campaign. A virus does not care and a virus does not feel. A virus just makes copies and reacts to the environment by acquiring new genetics. A virus escapes and evades. You are now being forced to drive your family directly into a hundred-mile wide, bone-dry forest in a three-year drought that has been primed by summer heat. From the moment you enter the expanse, you can feel the dryness of the stick wood and you know the logical outcome, but your route planners have given you no exit from this road. You can’t race this virus. One stray spark and everything changes.

On what type of journey do you wish to lead your family? Where on the scale between “Somewhat Unpleasant” and “Utterly Devastating” do you wish for your future rating to stand? Your actions today select your rating for tomorrow. This article provides you the initiative you need to act.

The route has been decided by our lack of determination, by our abdication of responsibility to untrustworthy people. Continue to Follow or Start to Lead, but be certain to load your vehicle well because your journey is beginning.

Glossary

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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2009-09-24

TamiFlu Shortage in Prime Risk Group Occurs Only 4 Weeks After School Starts

Children congregating in schools and universities appear to be the highest risk group for PF11 infection.  School has been in session for approximately 4 weeks.  Very little cold weather has occurred in the United States at this time.

Roche announced today that a shortage exists in their production of TamiFlu for children (liquid form).  The company advised pharmacists to grind the adult pill-based drug and adjust the dosage for children. 

Health officials say that priority will be given to those hospitalised.  If TamiFlu is effective only if used within 48 hours of symptoms and more than half of some populations do not present with the official case definition of fever, then few who are hospitalised will be within that 48 hour window.  Hospitalisation will primarily occur after significant viral replication time has passed (>48 hours) and the patient presents with incapacitating signals.  This prioritisation appears to be misguided given the Facts.

  • TamiFlu resistance is geographically widespread in PF11 as demonstrated in the sequence databases.
  • PF11 has not yet begun to peak. 
  • Public health officials expect cold weather combined with the school gatherings to spur the case count substantially.
These three material impacts on the pandemic combined with the early shortage of the primary mediation measure espoused by public health officials leaves the public with very few, publicly-messaged, viable options.

Please review our research section discussing proposed mediation measures for further information.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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2009-09-15

TamiFlu Resistance Database Expands, But Remains Incomplete. Two Year Pandemic Predicted.

Many TamiFlu Resistant cases have been reported that have not been sequenced and deposited in the United States and worldwide. 

Dr. Jonathan McCullers of St. Jude Children's Research Hospital in Tennessee reported a TamiFlu Resistant case yesterday, along with 12 child ICU cases and one child death.  Dr. McCullers indicates "a tremendous rise in cases" which began approximately one week after school resumed, well within the 3-10 day incubation period that we predicted post-congregation.  Dr. McCullers maintains that we are in the beginning of a two year pandemic that will have multiple peaks.  We agree that a period of 13 to 24 months from March 2009 is well within the expected duration.  Considering PF11's current position in the inter-species Influenza Flux and the high genetic variance demonstrated by the Hydra Effect, the lower boundary of our estimate (13 months) is unlikely unless the Case Fatality Rate increases significantly because PF11 rapidly depletes the population of potential hosts.

23 clinical observations have been publically discussed as TamiFlu Resistant in recent weeks around the world and most are not yet sequenced and deposited.  These cases concur with many of the geographic regions having sequences on file that match current TamiFlu Resistant sequences but for the H275Y.  In other words, the genetic acquisitions were predictable and expected to occur upon a proximal donor with 275Y co-infecting a host in that region.  An opportunity to review the full diversity of the anti-viral resistant strains would allow determination if, in fact, a silent spread of human-fit and reasonably transmissible TamiFlu Resistant strains is underway at this time or if we are seeing the improbability of an extensive and accurate selection due to treatment that is currently being purported as an explanation.  Evidence exists tending toward a silent spread, including that a substantial list is described with very early sampling and detection of H275Y, prior to any acceptable period for de novo / selective revision.  A minor sub-population of 275Y may be incorporated widely into the PF11 reservoir at this time.

The two youth in early July attending the North Carolina summer camp either spread their PF11 version one to the other or were each infected from a common carrier with a parental PF11 275Y Neuraminidase as is evidenced by the co-factor SNP on the NA of their sequences coding for 223V, known to amplify the 275Y TamiFlu resistance in H3N2.

We would like to thank those teams who have placed their sequences on deposit at GenBank and GISAID for the scientific community to evaluate.  The NA and HA for TamiFlu Resistant A/Singapore/57 from 2009-05-30 are again downloadable from the European EpiFlu database as GISAID has thankfully been able to re-establish access to their data.

TamiFlu Resistance is indicated in typical PF11 fashion via a Single Nucleotide Polymorphism on Singapore57 coding for 275Y on the Neuraminidase. The sequence displays the following NA Quadruple Combination:

106I, 248D, 275Y, 286S

The following permutations are now represented on the nine PF11 anti-viral resistant sequences:

106V, 248N, 275Y, 286S = WA28, WA29, TX47
106I, 248N, 275Y, 286S = Osaka180
106I, 248D, 275Y, 286S = HK2369, Yamaguchi22, Denmark528, Hunan SWL3, Singapore57

Until the 2009-08-21 deposit of the two Washington sequences at GenBank, all 275Y TamiFlu-Resistant specimens on PF11 backgrounds were paired with 106I. Today we see 3 of 9 with 106V.

The addition of Singapore57 re-leverages position 248 to Aspartate (D) with 5 specimens versus 4 with Asparagine (N).  No TamiFlu Resistant specimen on file displays 286G as yet.

A more robust database of sequences would be useful to invigorate the scientific community and the public in navigating this distant journey.

An n higher than 9 may assist us to align.


For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.



Please visit GeneWurx.com for insight into the latest published studies.

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2009-08-29

"Back to School" Early News Reports, including 25% Absenteeism

Washington State University, a campus of 19,000 students, reports 2,500 cases of Pandemic Influenza just days after the Fall Session started and projects 5,000 cases before this initial wave ends.

The University of Alabama reported 50 suspect cases on the first day of the session.  Several elementary schools in the southern United States have wisely closed to halt the spread of PF11 and protect their children.  Multiple reports crossing diverse geography exist of 10-15% absenteeism in the first week of elementary and middle school sessions.  Oak Mountain Middle School in Alabama (statewide high count of large population clusters), remains open with 25% absent. A group of elementary and middle schools in Pittsburgh remain open with 15% to 44% of the student population ill with Pandemic Influenza.

The chart represents a small sample from the hundreds of news reports available this week concerning the immediate and deep spread of PF11 in August as our children return to school.  




For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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2009-08-25

PF11 Trends & Issues, Mid-Term, Table of Contents

This analytical paper presented in a blog format attempts to synopsise more than one thousand point studies over a five-year period directed at Pandemic Influenza.  Revisions and updates will be made on this blog as the pandemic progresses. 

Read the sections first that most interest you and then return to read the complete work.  Using the ordered links in this Table of Contents will allow the reader a deeper comprehension as categorical terms are detailed sequentially at the point of introduction.

Please contact me with any concerns so that I may evaluate for revisions.
  1. Why should I care about Pandemic Influenza H1N1?
  2. What features does PF11 engage inside a human body?
  3. What human outcomes has PF11 demonstrated in this FirstWave?
  4. What part of our population is affected by PF11?
  5. What is the Nation Level Response to PF11?
  6. Where is PF11 going?
  7. Environmental Factors
  8. Genetic Acquisition Point Studies
  9. Glossary


Please visit GeneWurx.com for insight into the latest published studies.

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Environmental Factors

Our recent research has opened the door to a new segment of correlated history on plagues that may have been incorrectly categorized as the “Black Death” in the Middle Ages. The presentation and progression in the FirstWave and SecondWave of several ancient plagues are precisely equal to Pandemic Influenza clinical outcomes. The predecessor data directly relates 5 plagues throughout the 1300’s to the 1918 pandemic.

Dr. Thomas Francis, Jr., in a seminal immune response work, On the Doctrine of Original Antigenic Sin, returns us to the history of 1485 and the "sweating sickness" of England, then onward to the 1743 pandemic called variously "Blitzkatarrh" and "the Blue Plague" precursing the 1918 speed of rapid destructive spread in the population and the effect of human skin turning cyanotic blue from hypoxia (oxygen starvation).

On a side note, we may have located the geological event, an earthquake, in the early 1300’s that created a very large inland lake in China from which a plague proceeded therewith and where other plagues have begun in the past 700 years, potentially including PF51 (as yet undeclared Pandemic H5N1) and this PF11 currently circumscribing the globe. That area of research continues to be under review though the field may lead to no new information as very little surveillance data is available to collaborate the concept.

Famines have been highly correlated to plagues throughout history. We postulate that malnourishment of metabolic qualifiers, such as Essential Fatty Acids, B vitamins and vitamin C, reduces the body’s ability to properly feedback after an initial virally-induced Cytokinic Dysregulation. The famished body is left with no nutrients / anti-oxidants to re-regulate the feedback cycle of the immune response.

Without question, the United States suffers and leads the world with a population of malnourished and yet overweight individuals due to the reliance on non-food, processed factory materials for sustenance. An overweight human is at high risk for daily leptin imbalance, a form of Cytokinic Dysregulation. The excess adipose tissue is leptin-inducing, creating a ratio error in cell-to-cell signaling. That daily chronic signaling error may exponentiate in the face of this IDRRV Influenza. Consider the combination of malnourishment with high adipose tissue in the overweight and we may see a Cytokinic Dysregulation occur that does not have the nutrients to feedback and re-regulate, leading to rapid declines and fatal outcomes. Perhaps that cycle is the causality of the high mortality and ICU admittance in Michigan among the overweight?

No one knows where this Pandemic strain is going precisely; however, the standing data lead us to draw one certain conclusion. PF11 is consistently drawing acquisitions from the current Influenza genetic reservoir, acquisitions that appear stable in producing disturbing clinical outcomes and potentially escaping the vaccine target. At this point, too few surveillance points are available to make firm predictions, but a framework may be ascertained. Under that framework, the acquisition path of PF11 suggests a movement toward a foundation of human-specific seasonal Influenza SNPs that will then continue to aggregate changes from H5N1 and 1918 descendants.

Those 1918 descendants and the H5N1 strains concern all researchers and will certainly continue to inform our investigations.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

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Where is PF11 going?

No one knows as a certainty.

The “science” of Influenza genetics is far from well-developed concerning predictions. The literature remains peppered with phrases like "Surprisingly", "Unexpected" and "Data not provided" in areas that other studies claim to have proven; the "science" foundation for genetic prediction is yet small.  Most leading Influenza researchers are unwilling and unable to go on public record with vectors or potential paths of viral development. The “science” of Influenza and viral genetics is relatively young and though ground is being gained in the content arena, predictability using the current two pillars dogma is rarely undertaken because the protocols were built in an era that had only a low quantity of low quality data. New models of thinking and new protocols of investigation are required that incorporate the proofs demonstrated within the current reservoir of available data.

The recent high availability of PF11 sequences and clinical reports has given us data to understand where the virus is going, especially the much desired and appreciated sequences from South America shared by the Mailman School of Public Health at Columbia University. The sequences are from Argentina where the highest official death count in the world has caused healthcare rationing in all 77 hospitals in the socialized medicine system of Argentina. Many other countries in Latin America are refusing health services due to supply, personnel and infrastructure failures.

Genetic Acquisition Analysis

A managed campaign of political and laboratory messages in the media continues to state that no changes are found in Pandemic Influenza H1N1. The underlying genetics database, however, demonstrates many acquisitions and a consistent trend of fitness-inducing polymorphisms. As samples have been added each week around the world, a pattern has emerged.

The pattern indicates a persistent hyper-morphic state on the PF11 background at certain positions within particular species. Of certain note is the directional movement on the Hemagglutinin (variously termed HA and H1) and Neuraminidase (variously termed NA and N1) segments. Though all Influenza consistently recombines with existing genetic material from proximal non-self strains, PF11 has demonstrated a march toward human-fit acquisition that is remarkable in speed and geographic spread.

The purpose of these point by point studies is to indicate and discuss several of those key polymorphisms and examine the potential next steps in humans. As you have seen finally released in the media, PF11 in the human-form has now been sequence-confirmed in birds and in swine, allowing hundreds of species as additional “mixing vessels” or recombination reservoirs. This predicted species jump, more importantly, provides flight-based transportation vectors that will easily number in the millions of infected birds with a potential pool of billions in various seasons.

Recall the CDC reports that 70% of all emerging diseases are zoonotic (originate in animals). The asymptomatic flight-based animals transport the disease from their land-based counterparts, the swine, who are playing their normal role as ideal mixing reservoirs for recombination due to their robust tolerance to many strains of Influenza. Pig=>Duck=>Human=>Chicken=>Pig and dozens of additional paired vectors of transmission have been confirmed between human, swine and avian species. The genetic transition state between species, the Influenza Flux, is dangerous for humans due to continual creation of novel antigen and species-specific phenotypical traits that strain the human immune system, elevate the potential for vaccine escape and may produce a negative interplay with that nemesis of vaccine scientists, Original Antigenic Sin (OAS). 

OAS, in a few words, describes the physiological phenomenon observed since 1960 that antibody production to a novel virus is mediated and frequently downgraded by the priming epitope or first infection in an individual host from that species of virus (original childhood infection).  Frequent exposure to novel antigens within a virus species (notably Influenza), via vaccine and/or natural infection, tends to create fewer and fewer new antibodies that bind properly to the slightly dissimilar recent virus / antigen.  The documented process counter-intuitively invokes high-specificity memory B cells from the priming epitope (original childhood infection) which then feeds back signals to reduce the activation of naive B cells toward the new antigen.  Studies observe situations where Antibody Secreting Cells (ASC) produce antibodies to earlier infections in a ratio higher than antibodies to the new infection.

In short, PF11 at this time continues to create a Hydra Effect, attacking the human with many different heads or genetic variations.  The Hydra Effect coupled with the observed Interferon-Deranging Rapid Replication Viral (IDRRV) property creates a unique and daunting foe.

We will overview our findings on four gene segments with discussion on inter-segment correlations.




The reservoir of fitness-inducing polymorphisms available to PF11 is vast as we’ve determined 4 or more backgrounds in circulation that may have been slow, but consistent, donors to PF11.


 
The related reservoir has much more to offer in the coming months as the most important changes have either not yet been introduced or have not become fixed. Several of these candidate donor backgrounds are matches to provide one or more of the polymorphisms that have been demonstrated in the lab and shown clinically to strengthen Influenza against humans.

Remember that, although many are dying horrible deaths from PF11, this virus, as it stands today, is still most definitely hobbled / limited by many genetic shortcomings. The viral development process appears to be correcting those shortcomings by accepting consistent donations from the able reservoir of circulating Influenza strains worldwide.




We expect that PB2:627K (Increased Human Virulence) and NA:275Y (TamiFlu resistance) will be discovered widely in PF11. Relenza resistance is impossible to characterise at this time due to data paucity.

For a more complete and ongoing analysis, please read our PF11 Genetic Acquisitions studies.

For additional background on the clinical and epidemiological observational facts concerning Pandemic Influenza H1N1, please refer to the Table of Contents for PF11 Trends & Issues, Mid-Term.


Please visit GeneWurx.com for insight into the latest published studies.

GeneWurx.com