text:
The poll results were overwhelmingly against this idea. "No" received 88% of the vote.
I would vote "No" as well. There are only two reasons why BYU and Utah might attempt to arrange an annual bowl meeting:
1-They want to continue to play every year, but uncontrollable forces prevent it from happening during the regular season; and
2-They want to go back to a cold weather climate for the game, and the Pac-12 won't allow the game to be played in November.
Whether or not these are good reasons is very debatable. I only threw the idea out there as an attempt to blend a couple of themes filled with uncertainty right now: the possible new BYU bowl, BYU's long term bowl future, and the long term future of the Holy War. In the end, it presents a lot of challenges, and is probably too far outside the bowl box for fans to embrace it enough for it to be successful.
Thank you to everyone who voted. Don't forget to vote in this week's poll: "How should BYU football from 1986-1988 be viewed?"
The Editor appreciates all feedback. He can be reached via email at firstname.lastname@example.com


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Would you like to volunteer a little of your time to provide both social and practical help and friendship to the ex service community in Hull?
The partnership have opportunities for both men and women to become Befrienders, Case Workers, Social Inclusion,Admin and Promotions.
There are a wide range of volunteering opportunities including, Warehouse and distribution, Home maintenance, Social Inclusion, Child Care, Catering and Hospitality, Retail, Youth Work and Office and Clerical. for those who would like to gain skills for work and work experience available in other work areas.
Full training and support will be provided
For more info please contact: British Legion/Goodwin Partnership Trust
Email: email@example.com
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subset: commoncrawl


text:
In an eery coincidence firearms trainer John Farnham sent the follow email to one of our readers yesterday warning of the potential for another mass shooting at Ft. Hood:
New threat to American military bases:
Federal authorities are frantically searching for a self-professed Islamic jihadist, Muhammad Abdullah Hassan (aka "Booker"), who has threatened to duplicate the Ft Hood Massacre of November 2009. He was recruited by the Army, but then immediately discharged due to his threats. Agents interviewed him, but then inexplicably cut him loose, a move they now sincerely regret! . . .
Military posts around the Country have been put on alert. Who is going to protect all these defenseless, unarmed members of our so-called "armed" services from gun-wielding lunatics? The solution to this situation is too obvious, so it will be, once again, ignored completely by the promotion-conscious up our military food-chain: All officers and staff NCOs need to be armed all the time, on-base and off,concealed or openly. However, star-wearers are far more concerned about embarrassing, career-wounding NDs than they ever will be about dangers represented by armed madmen.
And, no one seems to want to train anyone in the art of actually carrying loaded guns on a routine basis. Big police department headquarters buildings are filled with armed men and women, and, yes, we have an ND now and then. But, we stay armed, and move on!
Since the Ft Hood incident in 2009, nothing has changed in this regard. "Gun-free zone" signs are still contemptuously ignored by violent criminals. The nerve of them! Our brave Soldiers, Sailors, Marines, and Airmen are still defenseless sitting ducks! As a nation, we are finally confronting the stark truth that we must have armed teachers in schools to protect children, but we still can't face the idea of armed soldiers protecting themselves!
Only in America!
John S. Farnam
36 Responses to BREAKING: Trainer Warned of Potential New Ft. Hood Shooter Before Incident
CNN and Fox both reported on this 2 days ago.
Mr. Diggler is correct … I saw those reports as well.
I read that two days ago
Anyone have an idea how many NCOs or Officers are stationed at the base?
I mean I am imagining a lot of M9s and 1911s could find use here, just curious how many.
You can only indefinitely detain US citizens under the NDAA and I believe there is a jihadist exclusion clause.
We had over 400 at Fort Bragg, combined I mean.
Fort Hood is MUCH larger personnel wise. The 2010 Census put them at around 53,416 and likely at least half of that is personnel stationed there, I don't know if that includes those off base or not but it gives you an idea of the size. http://en.wikipedia.org/wiki/Fort_Hood
Anybody else notice the last name. Where have we heard it before? Oh, yeah, same place 5 years ago.
LEO are told beforehand about BG's and bad things happen. How many times has this pattern occurred in the last 15 years? Are the same mistakes being made or are they consistently new ones?
Who could have ever imagined a US Army base as a huge gun-free zone….twice!!
I did not join the Army in 2002 because of the recruiter's response to my question "Do you shoot frequently?" His answer was: "I am not a violent man."
This told me everything I needed to know about how things would go.
News reports state that "Booker" can't be the shooter because he's been confined to a mental facility since last month. If true, the current shooter is someone else.
Reports also state that the shooter has been shot and killed. Who knows if that's true.
gun free ? how about the truck bomb in berute lebanon, when ronny reagon was president? 200 plus solders were killed. not the polocy to do garde duty with ammo for your m 16. how stupid then worse now. we dont want to offend anyone, but we are always a target.
Even when forewarned about the threat…
Just shows how unsafe our bases are, or how incompetent the brass is.
Incompetent, hell. They are experts at CYA and seeing through the fog covering the promotion road.
It also shows how easy it would be for a foreign military force to quite literally slaughter everyone at a base and render our military impotent. They wouldn't need more than 100 soldiers to secure the perimeter of a base and then another 50 to move through and promptly execute everyone.
And when you figure that there are only roughly 30 active military bases (of any strategic value) in the U.S., that means it would only take a force of about 4,500 soldiers to bring our domestic military to its knees.
On the other hand if our military bases actually operated as military bases and personnel were all armed, it would take a force at least 50 times larger to accomplish anything close to a complete annihilation.
This seems to happen at Army bases more than any other. In the 90's, Ft Bragg had a soldier shoot other soldiers at 0530 when they formed up to PT. Several rushed him and took the weapon.
There was shooting on the USS Mahan at Naval Station Norfolk last week. Ship security eliminated the threat quickly.
A ship is a lot easier to defend and protect than a base. People don't realize a base is the size of a small city. A ship you just have 2 armed guards patrolling at all times. And they can be within a minute of a threat at any given time. It's not really a fair comparison. But the fact the shooter even got on the ship says alot.
Sad news is this will just turn bases into an air port TSA screening station where everyone will have to go thru a metal detector strip down get a body cavity search before coming on base.
The secret about ships versus army soldiers is very simple. Ships and their major weapons are considered incredibly valuable, so sailors and marines can protect them with guns and live ammo. Soldiers? "We have lot of those, don't we?"
Again, the so-called "authorities" are directly told, in detail, to an immediate, lethal threat to the citizenry.
Again, the so-called "authorities" either deliberately ignore the warning or cut "their man" loose.
Again, the so-called "authorities" thought their fickle, impotent laws would protect them from madmen.
Again, they were wrong.
How shitty does the brass look with 3 mass shootings since 09 on base?
This rests squarely on the shoulders of the CO, all the way up to the commander in chief.
The report of 14 wounded does not fit with the report that it was a "soldier on soldier" shooting. They are making this seem a personal dispute, but if some guy was angry with another guy, it does not seem likely he shoots everybody in sight.
It sounds like they are going to try to pass this off as another "workplace violence" incident, the same old lie as the MAJ Hassan shooting.
The previous shooting by MAJ Hassan was "soldier on soldier" — the shooter was not a civilian.
Here is the policy.
Pay attention to #11 on page 2:
11. The Texas Concealed Handgun Law does not apply on Fort Hood. Concealed handguns are prohibited on Fort Hood.
All official firearms are unloaded and locked away in vaults.
How would requiring NCOS and Officers to carry guns solve anything? They have a police force. I imagine it would be not an easy task to maintain and account for all those guns being placed around base.
And if i recall the last shooter was an officer. Mandating people carry guns is an awful solution. A better solution would be to make military bases nothing more than a military base.
No hotels with maid service, No mcdonalds, No burger king…..No laundry mat………and no on base exchanges(Like in norfolk the navy exchange is off base so it's possible) we are stateside Why do we need all that on base? What would this solve… It would restrict access to bases to just military personal. IN addition to this they need to stop farming out the gate guards to citizens. Sure it's cheaper to hire civilians than to cycle thru new trainees every few years. But it's more regulated.
But even all this own stop shootings like this. Do you really think this guy thought he would live thru shootings on a military base?
You disgust me. "Soldiers defend themselves?! That's what the police are for!" How about we just lock the soldiers up in concrete barracks and only let them out for training and when we send them out to war? That way they'd be safe. Heck, why don't we do that for the rest of the country Too? Glorious future doesn't need decadent capitalist excess.
Often times soldiers who are very new are not allowed to go off base even when they do have down time, that along with the fact that many of the bases have families living there who can not or do not like to go to the towns near the bases is the reason why those services are needed. And it would not change anything when the bases are not as secure as you may want to think they are and it's personnel who are doing the shooting anyway.
I know for a fact that Ft. Sill is VERY insecure in some sections. I44 runs right through the base and at one point the only fence is a split wood fence you may see around a ranch style home with a car catch barrier cable. To have a car stop for a "flat tire" and drop people off would be WAYYYYY to easy. Ten steps from the car and they are on base, no security check and no knowledge of it. The base security has also been privatized so it's no longer MP's who stand watch but civilians who are cleet certified but often don't care.
"And if i [sic] recall the last shooter was an officer."
If I recall correctly, our best known traitor was General Benedict Arnold.
I'm all for putting into play the policy of "More guns, less crime" on our military bases.
Not related.
TWENTY-TWO THOUSAND, SEVEN-HUNDRED & TEN (22,710) worldwide terrorist attacks since 9/11 – all involving Islam. Yet, Obama's DOJ, FBI, DHS, Pentagon and State Department continue to give that genocidal death cult a pass. America better awaken soon for the camel's entire body is already in the tent.
What's with all the grammar and spelling mistakes in the posts lately? Quality over quantity please.
Its not like you're writing a scholarly article.
Good point. I should also have clarified that I actually meant the actual articles the TTAG staff is writing/posting are riddled with grammar mistakes lately. I could not care less about readers grammar and spelling.
Maybe if we put our heads just a little further up our own asses and ignore reality just a little harder, then maybe… just maybe we will be safe.
While there was a report a couple of days ago indicating that a man named "Booker" wished to commit jihad, that story also explained that "Booker" was slated to go to basic training on April 7. Therefore this is an entirely seperate incident.
Nesting boxes may be lined with wood shavings,
sawdust or even shredded paper. Depending on the climate as well as
the breeds, some hens yield even more or perhaps much less eggs


text:
Western Christian Schools begins at new Upland campus
There are 22 comments on the Inland Valley Daily Bulletin story from Sep 8, 2009, titled Western Christian Schools begins at new Upland campus. In it, Inland Valley Daily Bulletin reports that:The merging of Western Christian High School and Upland Christian High School was official Tuesday as the students, faculty and staff began a new school year together.
Join the discussion below, or Read more at Inland Valley Daily Bulletin.
#1 Sep 9, 2009
I wish the best for both Western Christian Schools and Upland Christian Academy as they are both giving students the opportunity to get a Christ-centerd education. After all, isn't that the reason for Christian schools?
Since: Aug 08
#2 Sep 9, 2009
It is so unfortunate how this all played out. The Anaheim District really dealt an underhanded blow to the Upland church and the school. Those affected will have scars on their hearts for a very long time. Upland Christian Academy Eagles of Rancho Cucamonga (change the name), you have all of my best wishes for a great first year! Go Eagles!
#3 Sep 9, 2009
Best of luck to Western and the Academy in Rancho as they educate our community's children in the Christian spirit. I so wish that all children could attend a Christian school and be immersed in God's love on a daily basis so that the children, and their families, grow in Christ.
Since: Nov 08
#4 Sep 9, 2009
Bankruptcy? This is the first I've heard.
Merger? Heard that one. I'm curious to see figures on how many students stayed and "merged".
Oh well. Good luck to UCA and WestUp.
#5 Sep 9, 2009
How many teachers & deans "merged"... formally employeed by UCS?
#6 Sep 9, 2009
When will people stop useing that word, it was NOT A MERGER!!!! IT WAS A SNEEKY TAKEOVER!!!
#7 Sep 9, 2009
Would you say UCS & UCA "merged"...
because ALL employed staff/ teachers/ deans/ office support/ daycare ect...ALL were Former employees at Upland Christian Schools...WAIT-----
I call that... Upland Christian...
They MOVED...They ARE somewhere else...
UCA IS Upland Christian Schools...
Correct me if I am wrong Western...who came over to your school? Just because you bought a campus does NOT make you anywhere close to being a part or merging with Upland Christian.
#8 Sep 10, 2009
Merger in the law is: "The fusion of absorbtion of one thing or right into another..."
Western purchased the rights to the name of Upland Christian School from its rightful owner, that being the Anaheim District.
So even if the "merger" isn't satisfactory to some, it happened. So let us be comforted by the way that God blessed UCA with a new campus and no debt.
I haven't been on this blog for many months, but after so after many months (one year almost) what else is there to chew on?
Proverbs 3:3-5
#10 Sep 10, 2009
Normally during a merger some changes occur and some are let go. Not all are let go. But then again Western can not be considered normal. The new article said UCA had like 360 kids. How many kids does Western have? Just curious.
#11 Sep 11, 2009
Acquisition and/or Purchase vs. Merger ...just look the words up, so we can all be on the same page.
Western Christian School (WCS) did purchase a building and rights to a name, but there is not a collaboration of things, which means its not a merger...Western is the name you see on their new gym floor, Western is the name that the kids wear on the polos...they are Western, not Upland. Western (WCS) is using their academic program, their faith, their old staff, teachers etc., it is Western Christian School.
And they did have security cameras added to Upland's campus before escrow closed, they did have teachers fired, they did stop the teachers from buying supplies and noted that nothing (including items purchased themselves) were to be taken from the premises, which also included all of the banners and trophies earned by Upland Christian students. So much of the blame may fall on Ray Doane the so-called 'leader' of the District of Anaheim of the Nazarene - but accountability of much does fall on Karen Winters and other representatives of Western Christian Schools....
#12 Sep 11, 2009
how many kids are attending western this year? neeeding info so I can decide where to send my kids next year.
#13 Sep 12, 2009
We have heard that Western's attendence grew this year to over 900 in the K-12 program (an increase of over 10% during a recession year). They have added programs, and improved the buildings on both campuses. The high school program has also grown. It appears that they are doing things God's way or they would not recieving the apparent blessings. Are they perfect - no - no one is, but from what we have seen and experienced (in the eight years we have been with the program) they are doing God's will. The UCA families may not like it - take it up with God - it is His will that Western is following.
Since: Nov 08
#14 Sep 12, 2009
according to the private school review (update 2/08)
wcs had 426 students pk-8 & 427 high schoolers.
120 Freshmen, 112 sophmores, 106 Juniors, and 89 Seniors.
So to be up over 10% over last year they would have had an enrollment drop last year. I don't have the numbers for last year though. It would certainly be interesting to see actual numbers for last year and this year.
#16 Sep 13, 2009
Well what I can tell you is that our 3rd grade grew by 10 students. That is in one grade alone. My son has already made a special friend who was previously a UCS student, yesterday he told me that he thinks God meant for them to meet....from the mouth of babes....everyone needs to move on and celebrate the fact that we continue to have choices in Christian education. I was very saddened to hear from a close friend whose daughter attends Sonrise Christian in Covina, that they had to close their San Dimas campus. Everyone needs to lift up our Christian schools in prayer, all of them!
#17 Sep 13, 2009
Answering my own question- According to the ASCI web site Western has 401 high, 96 jr high, 276 elementary, and 50 pre k. Now I do not know how accurate this is as that could be last years stats. They may not update frequently. I kind of find it hard to believe they have 401 kids in the high school but I guess any thing is possible.
#18 Sep 14, 2009
Sounds like last years figures. You can bet they would have
responded if you posted figures much lower than their numbers so 401 in the high school is probably way too high.
Allowing for a drop from the move, I'd bet it's closer to 300 high schoolers (maybe less).
#19 Sep 17, 2009
I think the question about enrollment is more about the high school numbers, it was my understanding that the K-8 has been and is still solid.
Does anyone know if the high school is the same, greater or less than?
#20 Sep 17, 2009
Call them up and ask how many they have.
Tell them you have a kid and are looking for a small school and classes. Then ask how many they got. I would but I am a big chicken
#21 Sep 17, 2009
the High School program had 399 students two weeks before school started and I've heard since then of two other students coming on board - equals 401. Last year we had 400 or so students. Which would indicate that even with the move and a loss as a result we also gained with the move to be about even with last year. This in a year when money is tight. I would say God is a work here.:)
Gods blessing upon both schools, Praise God we live in a country where we can make choices.
#22 Sep 17, 2009
Why do the Upland people care so much about Western's numbers? Wishing ill-will towards their Christian school hardly seems Christ-like. I pray you both have success--our communities need more, and stronger, Christian schools.
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Of course it probably helped that Harold [Brodkey] went to almost every literary party and spent hours on the phone every day with Don DeLillo, Harold Bloom, Dennis Donoghue. DeLillo told him the way to stop worrying about death was to watch a lot of television.
»Edmund White. City Boy : my life in New York during the 1960's and '70s. New York : Bloomsbury, 2009.
Month: March 2010
Flappers and flamingos
Kay Nielsen doing his Beardsley meets Erté thing. From In Powder and Crinoline : old fairy tales retold. By Arthur Quiller-Couch; illustrated by Kay Nielsen. [London] Hodder & Stoughton, 1912.
(Via Golden Age Comic Book Stories.)
A camera, not a chicken
Via Monoscope.


text:
|Publication number
|Publication type
|Application number
|Publication date
|Oct 19, 2004
|Filing date
|Jul 9, 2001
|Priority date
|Apr 11, 2000
|Fee status
|Also published as
|Publication number
|Avraham Oren, Yehuda Hartman, Yossi Fisher
|Original Assignee
|Insyst Ltd.
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (18), Non-Patent Citations (4), Referenced by (20), Classifications (11), Legal Events (8)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention relates to knowledge tree enablement within the medical field and more particularly but not exclusively to knowledge tree enablement in the field of studying side effects of drugs, with particular reference to liver toxicity.
Pharmaceuticals are required to undergo a demanding set of clinical trials in order to prove both that they work and that they work safely, that is without untoward side effects. Also, different pharmaceuticals interact with each other so that certain drug combinations cannot safely be prescribed. The interactions between drugs are not widely understood and there is a tendency not to prescribe in any case of doubt.
Clinical trials generally involve large numbers of patients and by their nature produce large amounts of data. The results of the trail are generally assessed and conclusions reached as to the safety and efficacy of the drug.
However, analysis of large amounts of data is difficult. Each patient or volunteer participating in the trial has a medical history and it is difficult to spot patterns in the data that relate, for example, to a particular item of medical history. Thus it is also known to use automatic methods of data mining, in which computers are used to find all the possible relationships within a data set. Such an approach is unhelpful in the case of clinical trials since many trivial relationships are found. Furthermore an enormous amount of processing power is required to run such data mining, and a large amount of human analysis is required afterwards to remove all of the trivial relationships and to concentrate on the important data
According to a first aspect of the present invention there is thus an automated modeler to modeling of an interactive system comprising at least one biological entity and at least one pharmaceutical substance, the system comprising:
a representation of states of the system,
an input, associated with the representation for allowing users to define at least one of, the states, expected relationships between the states and independent inputs to the states,
a data miner associated with the representation to operate on data taken from the system to apply the data to the states in accordance with the defined relationships and inputs, thereby to apply numerical values to the relationships and the inputs, thereby to model the interactions.
Preferably, the states include beneficial actions of the pharmaceutical substance.
Additionally or alternatively, the states include harmful actions of the pharmaceutical substance.
Preferably, the model is usable to predict harmful interactions of the pharmaceutical substance within the system.
Preferably, the interactions are between at least one biological entity and a plurality of pharmaceutical substances.
Preferably, the interactions are between at least one pharmaceutical entity and a plurality of biological entities.
Preferably, the data is clinical trial data.
Preferably the model is usable to direct a clinical trial.
Preferably, the model is usable to direct drug administration to a patient.
Preferably the model is further operable to use a second data set to calibrate the model, and a third data set to test the model.
According to a second aspect of the present invention there is provided an automated system for processing effects on liver toxicity of at least one pharmaceutical substance in application to a biological entity, the system comprising:
a representation of states of the application,
an input, associated with the representation for allowing users to define expected relationships between the states, and independent inputs to the states,
a data miner associated with the representation to operate on data taken from the application to apply the data in accordance with the defined relationships and inputs, thereby to apply numerical values to the interactions and the inputs, to model the application.
Preferably, the application comprises a plurality of pharmaceutical substances.
According to a third aspect of the present invention there is provided a system for producing likely liver toxicity as a side effect of application of a pharmaceutical substance, the system comprising:
an input device for obtaining blood levels of ALT and AST respectively,
a comparator, associated with the input device for comparing the respective levels of ALT and AST to produce a ratio of the levels, and
a predictor associated both with the input device and the comparator, for predicting, from the levels and the ratio therebetween, a likelihood of development of liver toxicity.
Preferably, the predictor is set to conclude from low ALT and AST levels and a ratio close to 1, that a likelihood of development of liver toxicity is low.
Preferably, the predictor is set to conclude from high ALT and AST levels, that a likelihood of liver toxicity is relatively high.
Preferably, the predictor is set to conclude from a ratio not close to 1, that a likelihood of liver toxicity is relatively high.
Preferably, the predictor is set to conclude from a ratio close to 1, that a likelihood of liver toxicity is relatively low.
A preferred embodiment further comprises a thresholder for setting a threshold likelihood, above which application of the pharmaceutical substance is to be discontinued.
According to a fourth aspect of the present invention there is provided a method for modeling an interaction between at least one biological system and at least one pharmaceutical substance the method comprising:
building a state diagram of the interaction,
entering at least one of inputs to the states and interactions between the states,
defining at least one output from at least one of the states,
obtaining empirical data regarding the interaction,
carrying out data mining on the empirical data to assign at least one of values to the relationships and functions to the states, thereby to obtain a quantitative model of the interaction.
Preferably, the method comprises
randomly dividing the empirical data set into at least two data sets,
performing the data mining using only one of the sets, and
testing the model using a remaining one of the sets to ensure that the data has not been overfitted.
For a better understanding of the invention and to show how the same may be carried into effect, reference will now be made, purely by way of example, to the accompanying drawings, in which:
FIG. 1 is a simplified diagram showing a modeling apparatus according to a first embodiment of the present invention,
FIG. 2 is a qualitative model for studying liver toxicity for use in the embodiment of FIG. 1,
FIG. 3 is an alternative qualitative model for studying liver toxicity for use in the embodiment of FIG. 1,
FIG. 4 is a further node for addition to either of the models of FIG. 3 or FIG. 4 for extending the model to control of a clinical trial,
FIG. 5A is a graph showing the relationship between ALT and AST liver enzymes in the blood.
FIG. 5B is a diagram of a knowledge tree that incorporates a linear relationship between the ALT and AST enzymes as inputs leading to a diagnosis, and
FIG. 6 is a simplified flow chart showing a method of modeling an interaction between a biological entity and a pharmaceutical substance according to an embodiment of the present invention.
Reference is now made to FIG. 1, which is a simplified schematic diagram of an automated modeler for modeling of an interactive system. An interactive system 10 comprises a biological entity and a pharmaceutical substance Generally, it is of great interest to understand the interactions within the system, so as to allow for safe use of the pharmaceutical substance. The modeler is initially supplied with a state model 12 of the system 10, generally as a logical entity within a computer. The state model may be specific to the system being tested or it may be generalized for a certain type of system. Generally, the number of states is small at least initially. As the problem is considered further it is generally broken down into smaller and smaller units. Thus the state model has a tendency to grow in size and the number of states increases. Initially, at an early stage of understanding it is often easier to work with a small number of nodes each having a large number of inputs and outputs, but as the model is refined, a larger number of nodes each reflect more direct causal relationships between a smaller number of inputs and outputs. The nodes at this more advance stage are easier to analyze in terms of data mining and the system tends to produce more accurate results.
Each node is preferably assigned a function that relates between inputs and outputs. At the start a presumed function may be used. For example a node may be defined for determining the quantity of bilirubin in the blood. There are two types of bilirubin, direct bilirubin and indirect bilirubin, each of which is measured separately. Each of the two measurements are set as inputs to the node and a summing function is set within the node to give an output indicative of the total amount of bilirubin.
Initially the function is either guessed or is fitted from the test data during the data mining procedure, a will be discussed in more detail below. The function is then refined using empirical data in an operation of function fitting. The function is preferably refined with empirical data to steadily reduce the output variance. As will be discussed in more detail below, overfitting of the function is preferably avoided.
The state model 12 comprises a representation of states of said system, but preferably does not initially include relationships therebetween, model inputs or quantities.
The modeler further comprises knowledge tree building 14, connected to the representation or sate model 12, for allowing users to define states in the model and expected relationships between the states and independent inputs to the states. The idea is that experts, persons expected to know about the system, are selected and asked to define relationships between the states, and inputs to the states, that they believe to be significant. Again, at this stage, no attempt is made to quantify and of the relationships. The experts are simply asked to define relationships that they believe, in the light of their experience, to exist.
In the present case, suitable experts may include pharmaceutical researchers familiar with trials of similar drugs, and specialist medical practitioners familiar with the condition that the pharmaceutical substance currently under test is intended to treat. It could include patients involved in the trial if deemed appropriate. Generally it is regarded as advantageous to apply as wide a range of experience to the input stage of the modeling as possible.
The modeler preferably has a database 16 of quantified information regarding the system to be modeled. Traditional modeling systems based on quantities of data have attempted to find every possible relationship within the data and have tended to produce unwieldy models and require processing resources out of all proportion to the data available and rising exponentially with increases in the size of the database.
A data miner 18 preferably operates in association with the representation and with the database to apply values to the relationships. That is to say the model, with its expert-defined relationships, is used as a guide to the data mining process. The data mining process is thereby restricted to the study of relationships regarded by experts as important or relevant and in effect, a dimension reduction is achieved in the modeling process. The result is a quantified model encompassing all the states and all the interactions therebetween that have been previously decided to be important. A further reduction in the model may then be carried out by removing relationships whose quantities are found to below a threshold value. Alternatively or additionally, relationships or inputs whose effect on an output is found to be negligible, may be removed.
In a further stage, if the model thus formed is found to be inadequate, the experts may be consulted again to find out if a relationship is missing. The quantification process may then be repeated with the new relationship. That is to say, when checking the data, the variance in the outputs is very large. In such a case a new relationship is preferably added to the model.
Returning to the question of function fitting, in theory it is possible to produce a function of very high order which covers exactly every single data point in the input. Such a function however is viewed as of limited predictive ability because it includes all the noise in the original data. Using functions of such high order is considered as overfitting the function. In order to prevent overfitting it is possible to randomly divide the data into three groups and to use the first group for initial quantization of the model, the second group for calibration of the model and the third group simply for testing the model. The third group is not used to refine the model but simply to ensure that the variance around the third group is the same as with the other groups, thereby determining that overfitting of the data has not occurred.
The system being modeled is generally the interaction between one or more biological entities and one or more pharmaceutical substances. A particular beneficial interaction may be the subject of the study or a particular harmful interaction, or the model may simply seek to model the interactions as a whole. Once the model has been created it may be used to predict possible interactions, including side effects, when administered to a patient. For example the model may contain a relationship between age and a particular side effect of the drug. The prescribing physician can therefore use the model to note that the danger of the side effect is enhanced and guide both himself and the patient as to particular effects to watch out for in particular cases. The physician is also provided with reliable information on which to base a decision that a particular drug is too dangerous to prescribe for a given patient or that, contrary to previous belief, a certain drug is perfectly safe to give to a particular patient. The latter case may result, for example, from the ability of the model to relate a particular side effect to age or any other patient variable, which the physician is then able to see is not applicable to his current patient.
The system may typically be used in a study of a single pharmaceutical substance used in numerous patients, that is to say is typical use its in modeling data from various stages of clinical trials. Subsequently the model may be used as a predictor in the use of the substance on individual patients. Of course the result of the treatment of the individual patient may then be added to the database for subsequent refinements of the model.
It is noted however, that the system may also be used for studying the use of a combination of drugs on patients. Generally, in such a case, interactions are poorly understood, and prescribing rules for drug interactions generally assume the worst. That is to say, if there is a known serious side effect of the particular drug combination then the physician will usually be led to avoid prescribing the combination in all circumstances. A predictive model that includes interactions between drugs may therefore serve as a means of allowing the prescription of a wider range of drug combinations.
The predictive power of the model may be used to direct a clinical trial. For example data gathered up to a certain point may reveal that the drug is harmful to patients over a certain age, and thus the trial may be stopped in respect of patients over that age but continued in respect of everyone else. Currently the trials are most likely to be stopped altogether.
A particularly preferred embodiment of the present invention uses a first set of data to build the model and then runs the model on a second set of data to calibrate the model. Preferably a third set of data if available, may be used to test the calibrated model.
Reference is now made to FIG. 2, which is a simplified diagram of a qualitative model for measuring liver toxicity effects of a drug. The model is the version after expert input but before data mining. The model contains two nodes, a first node 22 takes symptoms, signs and laboratory test results as input and produces an output of "type of hepatic dysfunction". A second node 24 receives the "type of hepatic dysfunction" as an input, along with previous patient history, severity of hepatic clinical function and serum levels of the drug, and produces an output of "potential for liver toxicity".
The model of FIG. 2 is from the point of view of the individual patient, and indicates a way of fixing the thought processes of the expert. The expert analyzes the patient clinical profile, which includes symptoms (subjective description of the patient's feelings) signs (objective marks on the patient's body) and laboratory test results, as described above. Using the patient's clinical profile the physician would normally decide on the diagnosis. More specifically, the physician may decide whether the patient has any hepatic dysfunction and refine the diagnosis concerning the liver The above process is embodied in the knowledge tree of FIG. 2.
The model as described above is sufficient to guide a data miner utility to create a formula for node 22.
Similarly node 24 includes four inputs as shown, serum levels of the drug, type of hepatic dysfunction, severity and previous history. The output of box 24 is the potential for liver toxicity of the specific drug. Following a similar analysis using a data mining utility the pharmaceutical company or prescribing practitioner is supplied with considerable information regarding the safety or efficacy of the drug.
Beyond relationships within individual nodes, the model also supplies information about relationships between nodes. Thus the output of first node 22 can be used as an input to second node 24. The relationship between the two nodes is that of cause and effect, which is to say that the output of the first node is one of the causes or inputs of the second node. It is pointed out that a cause and effect relationship can be examined in two ways, given a cause I can predict an effect, but additionally, given an effect I can use the tree to make assumptions about the cause. In the present case, moving from a final output of potential for liver toxicity one can determine the clinical finding in the patient that warned of the toxicity.
Reference is now made to FIG. 3, which is a simplified diagram of a variation of the model of FIG. 2. Parts that are the same as those in previous figures are given the same reference numerals and are not described again except as necessary for an understanding of the present embodiment. In the model of FIG. 3, a new node is introduced, of which "serum levels of the drug" is an output. Three inputs of dosage, distribution features and elimination features are defined as influences on the serum level. A progression is shown between the models of FIGS. 2 and 3 which progression is typical of how a model progresses as experts continue to deliberate over it.
Reference is now made to FIG. 4, which is a simplified diagram of an extension that may be made to either of the models of FIG. 2 or FIG. 3, to allow the model to be used in the management of a clinical trial. The model includes a single node 28 which receives as an input the output "potential for liver toxicity" of the models of FIG. 2 or FIG. 3. As additional inputs the node 28 is told about which phase of the trial is involved, the type of liver toxicity, and the severity of the liver toxicity. The inputs are for the clinical trial as a whole.
A series of outputs are defined as shown in the figure for managing the trail based on the information gleaned, continue or stop the trial, change drug dosage, new set of indications, new set of contraindications, change drug interactions, follow up patient more closely, and change environment.
Reference is now made to FIG. 5A, which is a graph showing a relationship that was discovered using the system of the previous embodiments and which can be useful to studying the state of the liver. In FIG. 5 the relationship is shown between two liver enzymes, ALT and AST. (Generally, levels of both ALT and AST are relatively low in the bloodstream as the enzymes are retained in the liver. In the event of trauma within the liver, and especially in the event of larger than normal scale death of liver cells, some of the enzyme escapes into the blood. Thus, the presence of noticeable levels of either of the above enzymes has been used in the past as an indicator of liver toxicity. Indeed in FIG. 5, the vast majority of points plotted are close to the origin of the graph. In applying the above embodiments to the liver system it was hypothesized that a linear relationship existed between the two enzymes. In any case a certain linearity can be seen in the graph.
The model found that there is indeed a linear relationship between the two substances, but that the linearity is stronger in the case of healthy patients than in patients already known to be suffering from liver dysfunction. Thus, the potential for liver dysfunction may be predicted by monitoring, not only the overall levels of AST and ALT, but also the extent of the linearity in the relationship therebetween.
For example a point numbered 33 located in the top right hand corner of the graph has high levels of both enzymes and would traditionally have been indicated as a sign of illness. Nevertheless the relationship is here shown to be linear, indicating that the illness is not serious. By contrast a point numbered 82 in the lower right part of the graph is very non-linear, indicating serious liver dysfunction.
The four numbered points 1202, 1039, 485 and 1664, around the periphery of the lower left region of the graph would traditionally have been regarded as being healthy on the grounds that neither enzyme is outside the limit. However linearity is clearly low and the present embodiment preferably signals the presence of liver disorder.
The above prediction may be incorporated into a model as described with respect to FIG. 4 for conducting a clinical trial. It may also be incorporated into an individual patient model of the kind shown in FIGS. 2 and 3. The model may be connected directly to an input device for reading in AST and ALT levels. Once the model has been quantized it will generally include a node whose outputs are defined so that they effectively compare the levels of the two drugs. If departure from linearity is detected then a diagnosis of liver disorder may be given. A knowledge tree which includes the enzyme levels as inputs and gives a diagnosis as an output is shown in FIG. 5B. Generally, the quantifying stage may find new relationships between variables or attach greater or lesser importance to previously known or suspected relationships, which can now be incorporated into new models.
It is also possible to build a dedicated device for applying to a patient to obtain an indication of liver toxicity. The dedicated device preferably comprises an input device for measuring AST and ALT levels and a processor includes comparison circuitry for producing a ratio. The processor preferably also includes analysis, or predictor, functionality which uses either or both of the absolute values and the ratio between to decide on the potential for liver toxicity. For example the predictor may be set to conclude from low ALT and AST levels and departure from the linear relationship, that a likelihood of development of liver toxicity is low. Likewise the predictor may be set to conclude from high ALT and AST levels, that a likelihood of liver toxicity is relatively high. Again, the predictor may be set to conclude from departure from linearity, without reference to absolute levels, that a likelihood of liver toxicity is relatively high. Likewise, the predictor may be set to conclude from a ratio close to linearity, without reference to absolute levels, that a likelihood of liver toxicity is relatively low. In a preferred embodiment, a thresholder may be included in the predictor for setting a threshold likelihood, above which application of the pharmaceutical substance is to be discontinued as being too dangerous. The threshold is preferably altered for different substances and for different ailments. For example a drug being used in life-threatening ailment is preferably assigned a high threshold for discontinuity whereas a drug that is being used for a chronic but low level condition may be given a lower threshold for discontinuity.
Reference is now made to FIG. 6, which is a simplified flow chart describing a method of modeling an interaction between a pharmaceutical substance and a biological system according to a preferred embodiment of the present invention.
In FIG. 6 a first stage of arranging a state diagram of the interaction to be modeled is carried out. Then a stage of adding interactions between the states and inputs to the states is carried out. At least one output is also preferably defined. The above stages are preferably carried out using a knowledge tree builder as described above. A data set, preferably including empirical data is taken to feed a data mining procedure which studies the data for the interactions indicated in the model. A quantified model of the interaction is thereby attained. Standard experimental procedure provides that the data is divided into three, preferably at random. One of the data sets is then used for data mining, one of the data sets is used for calibration and one of the data sets is used for testing the data to ensure that overfitting of the data has not occurred.
It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.
It will be appreciated by persons skilled in the art that the present invention is not limited to what has been particularly shown and described hereinabove. Rather the scope of the present invention is defined by the appended claims and includes both combinations and subcombinations of the various features described hereinabove as well as variations and modifications thereof which would occur to persons skilled in the art upon reading the foregoing description.
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|U.S. Classification
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|International Classification
|Cooperative Classification
|European Classification
|Oct 15, 2002
Owner name: INSYST LTD., ISRAEL
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:OREN, AVRAHAM;HARTMAN, YEHUDA;FISHER, JOSEPH;REEL/FRAME:013402/0141
Effective date: 20011011
|Mar 3, 2008
|Fee payment
Year of fee payment: 4
|Jun 4, 2012
|Maintenance fee reminder mailed
|Oct 18, 2012
|Surcharge for late payment
Year of fee payment: 7
|Oct 18, 2012
|Fee payment
Year of fee payment: 8
|May 27, 2016
|Maintenance fee reminder mailed
|Oct 19, 2016
|Lapse for failure to pay maintenance fees
|Dec 6, 2016
|Expired due to failure to pay maintenance fee
Effective date: 20161019


text:
Popcorn textured ceilings were most popular in the 1970s and 1980s but can also appear in newer homes. This bumpy ceiling treatment is easy to apply and inexpensive and often covers up blemishes on the ceiling. If you're ready to get rid of your popcorn ceiling, there's no need to call in the professionals. You, indeed even the novice do-it-yourselfer, can quickly remove a popcorn ceiling.
Things You'll Need
- Plastic sheeting
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- Rags
Protect the area you are working in with plastic sheeting to make clean up easier. Lay the sheeting down on the floor, then tape it all along the walls using painter's tape. Cover electrical outlets with plastic sheeting and painter's tape. Turn off the electricity to the room you're working in.
Fill an empty garden sprayer with warm water. Use a ladder to reach the ceiling and spray a 5 square foot section with the water. Make sure the section is completely wet, but don't saturate it.
Scrape off the popcorn texture with a 6-inch putty knife. Apply pressure to get off the texture but don't press too hard or you risk damaging what's underneath.
Continue this process, wetting a 5 square foot section then scraping off the popcorn, until all of the texture is removed. Spray more water on any spots that are tough to remove.
Wipe down the ceiling with a damp rag to remove any residue.
Tips & Warnings
- If your home was built in 1986 or before, or if you suspect the popcorn texture was applied in 1986 or prior, scrape off a small layer of the popcorn texture and send it to an EPA certified lab for testing. Don't scrape off the entire ceiling until you're sure it does not contain asbestos as this can be extremely harmful to your health.
- Wear protective eyewear and a dust mask on your face to avoid breathing in the dust from the texture and to keep dust out of your eyes.
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text: Small Acess Ability is a ability posessed by small characters in the Lego Indiana Jones: The Original Adventures. This ability is possesed by Maharaja, the Slave Child, and Short Round. The small acess hatches are marked by a small orange gate. These areas are used a lot in free play mode. but some are used in the regular game, but only in The Temple of Doom. To use these hatches, walk over to the hatch with a short character and press O.


text:
18591 Wilking Road, Fort Garland, Colorado
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18591 Wilking Road, Fort Garland, Colorado 81133 - Very clean little cabin like new. Off grid with solar power and a cistern for water. This cabin has easy access year round and has great views of Mt Blanca. Ojito Creek runs through the back of this 11 acres . This would make a great get a way spot for hunting seasons and summer vacations. Has a bonus camper that make s for a great guest house and the cabin comes all furnished, there is a little work to finish up on the plumbing. All the fixtures are in but the water lines need hooked up to the supply lines.
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text:
Sometimes, we focus too much on the negative. Good news just doesn't seem to get the same traction that bad news does. But as families gather around the dinner table to celebrate Thanksgiving, we at Voto Latino thought we would remember some of the many good things that happened this year, things that remind us that we're a democracy and that the people have power. The 10 items on this list show that government can work for the people and that the people can bring about change through action.
1. Online voter registration in California
In October, Gov. Jerry Brown signed into law the Online Voter Registration bill that allows Californians to register to vote through their county's election office website. Given that the primary reason people don't vote is that they miss registration deadlines, allowing people to register at the last minute from the comfort of their homes will lead to a more inclusive electorate. Now that's progress we can all cheer!
2. DREAM Act passed by states
While some states dedicated their resources to divisive laws that try to scapegoat immigrants, a handful of states this year recognized that investing in their young people's education, regardless of legal status, will help their economies thrive in the long run. California, Maryland and Illinois passed some version of the DREAM Act that will allow undocumented students to enroll in state colleges, and in certain instances, will extend financial aid opportunities to them. Great news, indeed.
3. Rep. Luis Gutierrez
We love elected officials who step up to lead a fight. And perhaps no one embodies that spirit today more than Rep. Luis Gutierrez of Illinois. From organizing tours around the country to highlight individual stories of suffering caused by deportations, to leading a congressional delegation to fight SB 56 in Alabama, Gutierrez has been an unflinching and steadfast advocate for hardworking immigrants. We hope more elected officials step outside of their DC offices to follow his lead.
4. Fight to Keep Families Together
States and cities across the country rejected a federal immigration program, Secure Communities, that requires police to send detainees' fingerprints for comparison against the FBI database. New York, Massachusetts, Illinois and the District of Columbia have told ICE they don't want to participate in the program because it is leading to the detention and deportation of too many people charged with minor offenses, including traffic stops, or even victims of domestic violence. ICE has said participation is not voluntary. Still, the actions by these cities and states has led to revisions in the program.
5. Same-day Voter Registration
In November, the people in Maine overwhelmingly voted to uphold same-day voter registration. With the "People's Veto," Maine overturned a law that had ended the 38-year-old practice of allowing voters to register on Election Day. Same-day voter registration makes it easier for people to vote, which we love. And the fact that the people protected it makes us love it even more.
6. Pearce recalled in Arizona
Arizona set off a national wave of laws hostile to immigrants and Latinos with the passing of SB 1070 last year. It turned out that the voters in Russell Pearce's district weren't pleased that their elected official was the author and one of the most ardent supporters of the law. Pearce used the national notoriety he achieved from promoting SB 1070 to secure powerful position of president of the state senate where he continued trying to pass even more restrictive anti-immigrant laws. But the people displeased with SB 1070 and his obsession with divisive laws didn't give up. They fought to get a recall election on the ballot and ousted Pearce from his seat. Si se pudo!
7. Occupy Wall Street Movement
We love seeing people actively involved in shaping the country's future. It's awesome to see OWS inspiring so many young people to speak out against the growing wealth inequality in the U.S. and challenge the relationship and influence corporations have with our government. People do have the power to change things, and movements like OWS breathe new life into the democratic process. We hope the next place these engaged people occupy is the ballot box.
8. DREAMers
Probably no movement is more coherent or active right now than the networks of people fighting for the DREAM Act. Through sheer people power, they have kept the DREAM Act going forward, winning legislation at the state level and petitioning to stop the deportations of DREAMers, including Matias Ramos, co-founder of United We Dream. The DREAMers seem to be everywhere: at Border Patrol offices challenging their failure to comply with a memo urging use of discretion to detain only immigrants with criminal records, and in Alabama, exposing themselves as undocumented and unafraid to show solidarity against HB 56.
9. Voter registration pep rallies
Pep rallies across the country are encouraging high school students to get civically engaged and register for voting. In McAllen, Texas more than 5,000 high school seniors were registered to vote in a celebration that resembled a pep rally. With more than 50,000 young Latinos turning 18 every month, it's more urgent now than ever that we organize voter drives like pep rallies to ensure that new voters are educated, engaged and empowered to hit the polls!
10. Social Media
Social media is enabling revolutions across the globe. Thanks to phones and gadgets, we are able to capture events as they happen, and within minutes spread, that information to millions across the globe. In February, we witnessed the Egyptian revolution. In August, there was the Libyan Civil War with thousands marching the streets of Tripoli. And most recently, we witnessed police brutality against students and peaceful protesters in the Occupy Wall Street movement. We love seeing kittens on YouTube, but seeing social media used to help democracy flourish is a lot more gratifying.


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Format: Paperback
Language: English
Format: PDF / Kindle / ePub
Size: 11.07 MB
Downloadable formats: PDF
Pages: 246
Publisher: CreateSpace Independent Publishing Platform (March 27, 2016)
Songs of the road
A Choice of Anglo-Saxon Verse
The Devine Comedy
The Psalms of Mortality, Volume 3: The Chameleon Persecutor Unmasked
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