text:
What's the Future of Newspapers? the Big Point Is This: There Is No Single Solution That Will Replace the Revenue Juggernaut That Has Been Newspaper Advertising. in Order to Survive, Newspapers Will Need to Realize That Some Combination of Small Solutions, Not One Big Gusher, Will Be the Revenue Model in the Future
Byline: Andrew B. Davis, SPECIAL TO THE WASHINGTON TIMES
There's been a lot of hand-wringing lately about the imminent demise of newspapers as we know them and what that will mean for our democracy.
But seriously, who cares? Newspapers are, after all, just technology - a platform for delivery of information. The real question should be, where will the money come from to support newspaper-quality journalism? And, if no one's reading newspapers, what will be the delivery mechanism and how will the audience for journalism access it?
In most typical daily newspaper markets, the number of people who read a newspaper has declined steadily since the 1970s and will undoubtedly continue to decline. However, most people are consuming more news and information than ever - they're just not picking up a dead-tree derivative to do it.
As long as some people want an ink-on-paper product, there will still be printed newspapers in some form, but most newspaper organizations have figured out they need to make information available however and whenever consumers want it, and they're working furiously to do that in innovative ways. I personally like the prospect of e-readers like Amazon's Kindle.
We need not worry about access to content.
What we do need to worry about is financial support for generating that content. Television and radio reporters and even the best of bloggers will all acknowledge that their work cannot substitute for the comprehensive, in-depth reporting and analysis that is done exclusively at newspapers, and that those functions are both critical and expensive.
Most of what is consumed as news begins today in print newspaper newsrooms. That free news content on Google started in those newsrooms. (Google employs no reporters.) Rush Limbaugh doesn't have a radio program without first reading the major national newspapers. Jon Stewart doesn't have a Daily Show without that print-originated news content as a backbone. Few bloggers do primary-source reporting. Even the Huffington Post would have to find another news source were there no newspaper content to aggregate and comment on.
Print advertising, which has heretofore paid the freight for that, is on the decline at the same time as fixed costs are on the increase, and newspaper profits are being squeezed to an unprecedented degree. Advertising won't support that kind of journalism in a digital future. So what's the solution? Charge for content online? A not-for-profit model like NPR? User micropayments? Other business service revenue streams?
Maybe, maybe, maybe and yes, and those are just some of the ideas. The big point is this: There is no single solution that will replace the revenue juggernaut that has been newspaper advertising. In order to survive, newspapers will need to realize that some combination of small solutions, not one big gusher, will be the revenue model in the future.
This leads to the harsh realization that the revenue lost from traditional advertising will never be completely replaced. Newspaper companies will become smaller. …


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This Stübben Equi-Soft® Dressage Girth helps solve girthing problems that detract from a horse's performance. This girth is designed to prevent constriction with an ingenious system of elastic rings that provides perfect pressure distribution and a revolutionary shape allows the expansion of the horse's chest during exertion.
The Walsh™ Fleece Girth with premium fleece and extra padding within provides comfort for your horse. Durable and attractive, this girth goes from the schooling ring to the show ring. Constructed with nylon chapes, heavy-duty elastic ends and a center D-ring.
The PJ Stabilizer Girth boasts a classic overlay and a contoured shape for horse comfort. It's made of top-quality leather and fitted with a carabiner clip.
From Tory Leather Company, the Deluxe Leather Girth Loop makes it easy to attach training aids.
This Total Saddle Fit Dressage Girth Cover is perfectly shaped in 100% sheepskin to line the Total Saddle Fit Dressage Girth. Natural sheepskin promotes air circulation, provides cushioning and pulls moisture away from your horse.
Designed for comfort, the Schockemohle Canter Elastic Girth in quality neoprene has a nylon inner surface and rounded edges. Elastic at one end and stainless steel roller buckles allow for easy tightening.
The Stubben Fancy-Stitched Girth has a beautiful overlay with subtle fancy-stitched detail. In high-quality leather that's padded for your horse's comfort, this classic leather overlay girth is fitted with Stubben's flat stainless steel buckles that eliminate bulk.
Affordable, classic-looking and comfortable, the HDR Fleece-Lined Overlay Girth pairs a fancy-stitched leather overlay with a removable, washable synthetic fleece lining. This girth has double elastic ends, roller buckles and a center D-ring.
Grimy leather is easily cleaned with Bick 1 by Bickmore®. This aggressive leather cleaner is formulated to remove soil, grease, spur marks and most stains from smooth leather. Follow cleansing with Bick 4 Leather Conditioner for best results. 8 oz.
The Professional's Choice® VenTech™ Fleece Combo Girth promotes cooling airflow with a removable strip of VenTech material next to your horse's skin. Synthetic fleece adds to your horse's comfort. This unique girth has elastic at both ends, stainless steel roller buckles and a center D-ring.
The Schockemohle Contoured Jumper Girth has a protective wide belly area with a center carabiner type fastener for training aids. Stainless steel roller buckles with recessed grooves for the buckle tongues make for a bulk-free fit under the leg. This leather jumper girth has two D-rings at the sides.
PDS™ Gullet Plates enable riders to quickly and easily change the width of the carbon fiber tree inside PDS saddles.
Make your straight girth more comfortable for your horse with this Shires SupaFleece Girth Sleeve. Soft, thick and breathable, this girth sock acts like real sheepskin, but is easier to care for, more affordable and dries fast.

subset: commoncrawl


text: Obama: No, I Didn't Storm Out Of The Debt Ceiling Talks (VIDEO) ByEvan McMorris-SantoroPublishedJuly 14, 2011, 9:50 PM EDT Hey, remember when House Majority Leader Eric Cantor said President Obama walked out of the debt talks yesterday? So, yeah -- Obama says that never happened."No," Obama told Cox TV's Scott McFarlane in an interview Thursday. "At the end of the meeting, what I said to the group was what the American people feel: We have a responsibility to do the right thing. We shouldn't be partisan, we should solve problems." The interview was one of a few sit-downs Obama did with local television reporters from across the country today. In addition to the interview with McFarlane, he spoke to TV stations in Philadelphia and Washington, DC. Watch the raw, uncut Cox TV interview below:


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text:
Freedy Johnston
Come for the voice, stay for the lyrics. Freedy Johnston's luminescent Kansas-Hoboken plainness would suit either the country or R&B he skirts, if not the bossa nova he adores, because his inflection-free emphasis on lovely pop melodies transcends persona. That leaves his unreliable narrators more vivid: "Don't Fall in Love with a Lonely Girl," off his new album recorded in Nashville, Rain on the City, is catchy romantic doom as Juliana Hatfield might imagine it, while "Livin' Too Close to the Rio Grande" is a great road/river song ("Between the wife and the ex and the government...I never met a dollar that wasn't spent") informed by the soulful ease he otherwise displays on "The Devil Raises His Own." None of those might be essential to non-fans the way his '90s hit "Bad Reputation" or sophomore album were to many, but they enrich a live greatest-hits worth catching, this time at a venue that guarantees intimacy. If the grownup Taste of Minnesota hecklers pay their way in, Johnston will have to challenge them to a bowling game.
Thu., Jan. 21, 9:30 p.m., 2010
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text:
Tasleem's Group
She has applied for a loan from Kiva partner Asasah because her husband wants to buy another buffalo to expand his dairy business. By purchasing another buffalo, he will be able to increase the milk production to sell to more customers to earn better profits. Tasleem is hopeful that a loan will help her husband make more profits and improve the living standards of his family. She is a new loan applicant and this is her first loan application to Asasah.
Note: In the photo, the lady with a book (called Asasah Passbook) is Tasleem.
Additional Information
This is a Group Loan
In a group loan, each member of the group receives an individual loan but is part of a larger group of individuals. The group is there to provide support to the members and to provide a system of peer pressure, but groups may or may not be formally bound by a group guarantee. In cases where there is a group guarantee, members of the group are responsible for paying back the loans of their fellow group members in the case of delinquency or default.
Kiva's Field Partners typically feature one borrower from a group. The loan description, sector, and other attributes for a group loan profile are determined by the featured borrower's loan. The other members of the group are not required to use their loans for the same purpose.
About Pakistan
267View loans »
Success!! The loan was 100% repaid
- Repayment Term
- 13 months (Additional Information)
- Repayment Schedule
- Monthly
- Pre-Disbursed:
- Apr 14, 2011
- Listed
- Apr 18, 2011
- Currency Exchange Loss:
- Possible
- Ended:
- Apr 15, 2012


text:
If you need Aerobics or Fitness or even Exercise in NV, look no further. www.hotfrog.com showcases more than 16 Aerobics businesses across NV. To find more related businesses and to filter by locality, use the left navigation menu.
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Great Senior Fitness promotes longevity and healthy aging by offering senior exercises with exercise videos and fitness instruction for seniors, including brain exercise, chair exercises, stretching and aerobics. Exerci…
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European Fitness Center Reno Nevada - Exercise in our Gym, Aerobics and Spa areas,State of the art fitness equipment, classes with onsite resturant, hair and nail salons
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Super Kids Karate is a non profit organization dedicated to developing strong confident individuals through Taekwondo. Super Kids Karate has been in the Las Vegas area since 1994
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text:
I'm remodeling my bathroom and taking advantage of the open walls to replace the supply and DWV lines in that part of my 70 year old house. My neighbor had all of his plumbing replaced a few years ago and the plumber went all the way to the roof with the new vent line. My roof is slate with a number of years of useful life left and I would rather not replace the stack that far and risk causing a leak in the temperamental roof. My preference is to add new line only from the point where the drain line enters (about 4' below the roof) and downward from there (using a no-fitting), thus not disturbing anything within a few feet of the roof. My simple mind tells me this should be fine. Are there any potential problems that I am missing?
I would do the same thing. The only thing I would make sure I do, is to bolt the pipe rigidly before I cut it. Most plumbers typically use either a riser clamp or metal band iron (this is thin metal 1/2" wide about 16 ga with holes in it). The riser clamp is the best because its very rigid support. The band iron, can be bolted to the pipe with 1/4" or 3/8 inch bolts and nuts right through the holes. You unrole about 3' of band iron and cut it with snips, do that twice. Then in the middle of the band iron set it aginst the pipe on both sides. Wrap it till each piece of band iron is touching, leaving about 1' on each side. Then bolt the two pieces of band iron together on each side of the pipe. Make sure to clamp it so the bolts sinch the band iron tight against the pipe like a clamp. You should have four 1' ears extending away from the pipe. Make them all 90 degrees apart and screw them with lags to the beams in the roof. Do this at two different locations and the pipe will be rigid when you cut it.
Good Luck
Raymond VinZant Plumbing Prof.
Good Luck
Raymond VinZant Plumbing Prof.
vent pipe noise
Roof Vent
Distance from vent pipe
Vent stack problem
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text:
|Publication number
|Publication type
|Application number
|Publication date
|Apr 15, 1997
|Filing date
|Oct 5, 1994
|Priority date
|Oct 5, 1994
|Fee status
|Publication number
|Robert F. Garry, Scott A. Tenenbaum, Douglas R. Plymale
|Original Assignee
|Administrators Of The Tulane Educational Fund
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (2), Non-Patent Citations (24), Referenced by (1), Classifications (30), Legal Events (4)
|External Links: USPTO, USPTO Assignment, Espacenet
The present invention is directed to a process and a kit for diagnosing silicone related disease (SRD). The process comprises obtaining a sample of body fluid from a patient and testing the sample for the presence of anti-polymer antibodies reacting to partially polymerized acrylamide as an antigen. The presence of anti-polymer antibodies indicates SRD if the patient has a polymeric implant, or a pre-disposition to SRD if the patient has no implant.
Silicones are entirely synthetic polymers containing a repeating silicon-oxygen (Si--O) backbone with organic groups attached directly to the silicon atom through a carbon bond. The most common form of silicone is polydimethylsiloxane (PDMS) and has a repeating unit of (CH3)2 SiO.
Silicone polymers have, until recently, been considered biologically and immunologically inert, and for this reason are included as exterior coatings or components of most medical devices that are surgically implanted into humans. Some examples of silicone-containing devices include hip replacements, catheters, mandibular prostheses, and breast implants. It is estimated that more than 2 million women in the United States have been recipients of silicone implants for augmentation mammoplasty and breast reconstruction following cancer surgery.
However, as devices such as silicone breast implants have become more widely used, there has arisen increased concern that silicone may be neither biologically nor immunologically inert. Silicone can be formed into fluids, gels or solids based on the degree of linear, branched, and cross-linked subunits. The degree of crosslinking dictates the consistency of the resulting silicone, which can vary from a clear gel to a white opaque elastomer. The crosslinked polymers form a loose intertwining matrix which retains the remaining silicone fluid. The lack of chemical integrity of this complex is suspected to permit "gel bleed" of silicone fluid slowly out of the matrix. Impurities such as catalyst, short linear polymers and small cyclics can remain depending on the stringency of the purification technique employed.
Approximately 10% of patients who receive medical devices containing silicone polymers experience complications including inflammation, severe muscle pain, or overt rheumatic (autoimmune) disease. Recently, silicone implants have been linked to multiple sclerosis-like symptoms, particularly in patients whose implants have ruptured. Yet, a portion of the approximately 2 million women in the United States who have received silicone gel filled breast implants have complications such as infection, capsular contraction, leakage, and rupture (Touchette, 1992). Additionally, some breast implant recipients experience a syndrome characterized by symptoms which include fibromyalgia, sicca syndrome, lymphadenopathy, contracture, sclerodactyly, alopecia, edema, telangiectasias, changes in pigmentation, recurrent fever, skin rash, and chronic fatigue (Brozena et al., 1988; Seleznick et al., 1991; Vasey et al., 1991; Copeland et al., 1993; Spiera and Kerr, 1993; Spiera et al., 1994). This syndrome, which also afflicts recipients of other silicone-containing medical devices, was previously termed human adjuvant disease (HAD) (Miyoshi et al., 1964; Miyoshi et al., 1973). Individuals surgically implanted with various devices containing silicone may also develop arthritic and dermatologic conditions that present autoimmune-like diseases, such as systemic sclerosis (scleroderma) or Sjogren's syndrome (Brozena et al., 1988; Vasey et al., 1991; Spiera et al., 1994). Studies implicating silicone-containing medical devices in autoimmune diseases, however, have been met with considerable skepticism (Gabriel et al., 1994).
Complications occurring after implantation of silicone-containing medical devices may generally fall in two categories:
1 ) Atypical Connective Tissue Disease (ACTD)/Atypical Rheumatic Syndrome(ARS)/Nonspecific Autoimmune Condition (NAC). Symptoms include tightness of skin, contracture, sclerodactyly, alopecia, oedema, telangiectasias, rash, and changes in pigmentation. These symptoms have been frequently associated with silicone breast implants, but occur also in recipients of other silicone-containing medical devices.
2) Overt autoimmune diseases. Some investigators have reported that recipients of breast implants are more likely than non-implanted individuals to develop autoimmune diseases such as systemic lupus erythematosus or scleroderma. Increased levels of previously defined autoantibodies (SS-A, SS-B, Sm, etc.) have also been observed.
Exposure to silicone breast implants can result in the manifestation of symptoms and complications that collectively are dissimilar from previously recognized or defined rheumatological diseases, and therefore, may be uniquely identifiable with the appropriate diagnostic tests. Nevertheless, the systemic nature and relatively nonspecific symptoms of the diseases, particularly undifferentiated rheumatic diseases and SRD, often make the diseases difficult to diagnose and difficult to distinguish. An assay method which would enable the clinician to distinguish and discriminate between undifferentiated rheumatic diseases and SRD is highly desired.
Surgical implants have benefits that extend from prolongation of life to cosmetic enhancement. Implants also have associated risks, and these unknown risks motivate some people to forego implants, even though the benefit may outweigh the risk. Likewise, removal of existing implants may involve expense, pain, disfigurement, disability and death. A diagnostic test that would help an implant candidate balance the benefit and the risk of his/her implant is badly needed.
The present invention is directed to a process and a kit for diagnosing silicone related disease (SRD). The process comprises obtaining a sample of body fluid from a patient and testing the sample for the presence of anti-polymer antibodies reacting to partially polymerized acrylamide as an antigen. The presence of anti-polymer antibodies indicates SRD if the patient has a polymeric implant, or a pre-disposition to SRD if the patient has no implant.
Additional objects, features, and advantages will be apparent in the written description which follows.
In characterizing autoimmune responses in various systemic autoimmune diseases, including scleroderma, Sjogren's Syndrome, and systemic lupus erythematosus (SLE), we use immunoassays. Immunoassay techniques are extremely sensitive and specific, and in using these methods we identified a novel polymeric antigert that is recognized by serum antibodies from over 50% of persons with silicone breast implants who display systemic "autoimmune-like" symptomatology. We have developed an extremely sensitive immunoblot assay (Line blot) that is capable of detecting these anti-polymer antibodies (APAs). Our results indicate that an APA immunological response may contribute to complications from implanted silicone polymer-containing devices.
These results provide the first definitive evidence that silicone breast implants are capable of inducing an immunological response that is diagnostically testable. The detection of this immunological response provides us with a unique opportunity to develop a serological test that has broad clinical applications.
Anti-polymer antibodies appear to be a reliable predictor of the autoimmune-like complications associated with silicone breast implants. Our work is the first study to provide an unarnbiguous result indicating that silicone is not immunologically inert. Our results also identify a distinguishing feature that may be of diagnostic and prognostic value in treating these individuals. Moreover, our results form the basis for a test that if properly developed could find wide-spread medical and commercial use in the biotechnology industry. The test could be used to monitor immunological responses to silicone-containing medical devices. In the future, this is likely to be an important criterion for devices used in the medical industry. This could afford the development of alternative polymer forms of silicone specifically formulated so as not to elicit immune reactivity.
Surgical implants have benefits that extend from prolongation of life to cosmetic enhancement. Implants also have associated risks. It is known that some people produce anti-polymer antibodies, but do not have implants. In those people, placement of an implant might aggravate latent problems that are manifested by anti-polymer antibodies. The anti-polymer test can help implant candidates to evaluate risk associated with their implant and to decide either to forego the benefit to avoid the risk, or to accept the risk to obtain the benefit.
For those people who already have implants, the test would be useful in determining whether to remove the implant. A negative anti-polymer test would provide some assurance that the risk is at least not immediate, and with continued monitoring the pain, expense, disfigurement and medical risk of surgical removal could be avoided. A positive test would provide some assurance that removal is appropriate.
Before proceeding further with the description of various specific embodiments of the present invention, a number of terms will be defined. A variety of assay techniques in which the object of the present invention can be achieved are also described.
The term "analyte" refers to either the polymer antigen or the anti-polymer antibody.
As used herein, "test sample" or "body fluid sample" typically refer to a naturally occurring or artificially formed liquid test medium suspected of containing the analyte of interest. The test sample is generally a biological fluid or a dilution thereof. Biological fluids from which an analyte can be determined include serum, whole blood, plasma, body fluid, saliva, amniotic and cerebrospinal fluids, and the like.
The term "indicator reagent" refers to an assay reagent comprising a detectable label directly or indirectly attached to a specific binding member which is capable of directly or indirectly binding to the analyte to indicate the presence, absence or amount of the analyte. A variety of different indicator reagents can be formed by varying either the label or the specific binding member. In general, the indicator reagent is detected after it has formed a complex with either the analyte or a complementary specific binding member, but the unbound indicator reagent can also be detected.
The term "specific binding member" refers to a member of a specific binding pair, i.e., two different molecules wherein one of the molecules through chemical or physical means specifically binds to the second molecule. In addition to antigen and antibody specific binding pairs, other specific binding pairs include biotin and avidin, carbohydrates and lectins, complementary nucleotide sequences, complementary peptide sequences, effector and receptor molecules, enzyme cofactors and enzymes, enzyme inhibitors and enzymes, a peptide sequence and an antibody specific for the sequence or the entire protein, polymeric acids and bases, dyes and protein binders, peptides and specific protein binders, protein A and antibodies, protein G and antibodies, and the like. Furthermore, specific binding pairs can include members that are analogs of the original specific binding member, for example an analyte-analog. If the specific binding member is an immunoreactant it can be, for example, an antibody, antigen, hapten, or complex thereof. If an antibody is used, it can be a monoclonal or polyclonal antibody, a recombinant protein or antibody, a mixture(s) or fragment(s) thereof, as well as a mixture of an antibody and other specific binding members. The details of the preparation of such antibodies and their suitability for use as specific binding members are well-known to those skilled in the art.
The term "label" refers to any substance which is attached to a specific binding member and which is capable of producing a signal that is detectable by visual or instrumental means. Various suitable labels for use in the present invention can include chromogens; catalysts; fluorescent compounds; chemiluminescent compounds; radioactive labels; direct visual labels including colloidal metallic and non-metallic particles, dye particles, enzymes or substrates, or organic polymer latex particles; liposomes or other vesicles containing signal producing substances; and the like.
The term "signal producing component" refers to any substance capable of reacting with another assay reagent or the analyte to produce a reaction product or signal that indicates the presence of the analyte and that is detectable by visual or instrumental means. "Signal production system," as used herein, refers to the group of assay reagents that are needed to produce the desired reaction product or signal. For example, one or more signal producing components can be used to react with a label and generate the detectable signal, i.e., when the label is an enzyme, amplification of the detectable signal is obtained by reacting the enzyme with one or more substrates or additional enzymes to produce a detectable reaction product.
The term "capture binding member" refers to a specific binding member which can directly or indirectly bind the analyte or indicator reagent and which is bound or is capable of being bound to a solid phase, or is capable of being precipitated, such that the capture binding member can be separated from the test sample and other assay reagents by any means. The term "capture reagent" refers to a capture binding member which is directly or indirectly attached to a solid phase material to enable the separation of the capture binding member, and analyte or indicator reagent that is bound thereto, from unbound analyte and assay reagents. Typically, the attachment of the capture binding member to the solid phase material is substantially irreversible and can include covalent mechanisms. The capture reagent of the present invention, however, is not limited to a capture binding member bound to an insoluble solid phase material. In an agglutination assay, the capture binding member of the capture reagent can be bound to a soluble carrier material such as bovine serum albumin.
The term "solid phase material" refers to any suitable chromatographic, bibulous, porous or capillary material or other conventional solid material, well-known to those skilled in the art, used to immobilize specific binding members. In the present invention, the solid phase material can include a fiberglass, cellulose or nylon pad for use in a flow-through assay device having one or more layers containing one or more of the assay reagents; a dipstick for a dip and read assay; a test strip for chromatographic (e.g., paper or glass fiber) or thin layer chromatographic (e.g., nitrocellulose) techniques in which one or all of the reagents are contained in separate zones of a single strip of solidifies material; or an absorbent material well-known to those skilled in the art. The solid phase material can also include, without limitation, polyacrylamide beads, polystyrene beads or tubes, magnetic beads, a microtitre plate or a glass or plastic test tube.
Natural, synthetic, or naturally occurring materials that are synthetically modified can be used as a solid phase material. These materials include polysaccharides, cellulose materials such as paper and cellulose derivatives such as diazobenzyloxymethylcellulose, nitrocellulose, 2-aminophenylthioetheylcellulose, and cellulose acetate; silica; silicon particles; inorganic materials such as deactivated alumina, or other inorganic finely divided material uniformly dispersed in a porous polymer matrix, with polymers such as vinyl chloride, vinyl chloride polymer with propylene, and vinyl chloride polymer with vinyl acetate; cloth, both naturally occurring (e.g., cotton) and synthetic (e.g., nylon); porous gels such as silica gel, agarose, dextran, and gelatin; polymeric films such as polyacrylates; protein binding membranes; and the like. The solid phase material should have reasonable strength or strength can be provided by means of a support, and it should not interfere with the production of a detectable signal.
Blocking is a term that describes procedures used to prevent nonspecific adsorption of immunological reagents to a solid phase material. Blocking methods are well known to those skilled in the art.
Optionally, the specific binding member of the capture reagent can be affixed to particles, e.g., microparticles. These microparticles can serve as the solid phase material and be retained in a column, suspended in a mixture of soluble reagents and test sample, or retained and immobilized by another solid phase base material. By "retained and immobilized" is meant that the microparticles associated with the solid phase base material are not capable of substantial movement to positions elsewhere within that material. The microparticles can be selected by one skilled in the art from any suitable type of particulate material including those composed of polystyrene, polymethylacrylate, polypropylene, polytetrafluoroethylene, polyacrylonitrile, polycarbonate, or similar materials. The size of the microparticles is not critical, although it is preferred that the average diameter be smaller than the average pore size of the solid phase base material if such is used.
The homogeneous assay configurations do not require the separation of the test solution and the indicator reagent prior to the detection of the indicator reagent or binding complexes. This broad classification includes many formats such as agglutination and precipitation assays, as well as others known to those skilled in the art for the detection of analytes. Both direct and indirect agglutination assays can be performed.
The term "ancillary specific binding member" refers to a specific binding member used in addition to the capture binding member and the indicator reagent which becomes a part of the detectable binding complex. One or more ancillary specific binding members can be used in an assay. For example, an ancillary specific binding member can be used in an assay where the indicator reagent is capable of binding the ancillary specific binding member which is in turn capable of binding the analyte.
The homogeneous assay configurations do not require the separation of the test solution and the indicator reagent prior to the detection of the indicator reagent or binding complexes. This broad classification includes many formats such as agglutination and precipitation assays as well as others known to those skilled in the art for the detection of analytes. Both direct and indirect agglutination assays can be performed.
The object of present invention can be achieved by a variety of binding assay configurations and formats which enable the detection or measurement of APA antibody to diagnose, stage or predict the course of rheumatic disease. The APA antibody were found to be readily detectable in urine samples by means of binding assays which are generally categorized into one of two major classes, homogeneous and heterogeneous assays. These assays may be further divided into sandwich and competitive assay formats, and variations thereof.
In a solid phase sandwich assay, the capture reagent typically involves a specific binding member which has been bound to a solid phase material. For example, the specific binding member can be an immobilized antibody which will bind to an antigen-analyte in the test sample, or the specific binding member can be an immobilized antigen which will bind to an antibody-analyte in the test sample. The capture reagent is contacted to a test sample suspected of containing the analyte, and to an indicator reagent comprising a second specific binding member that has been labeled, for example, a labeled anti-analyte antibody. The reagents can be mixed simultaneously or added sequentially, either singly or in combination. A binding reaction results in the formation of a capture reagent/analyte/indicator reagent complex immobilized upon the solid phase material. The assay can also comprise the step of separating the resultant complex from the excess reagents and test sample. The complex retained on the solid phase material is detected by examining the solid phase for the indicator reagent. If analyte is present in the sample, then label will be present on the solid phase material. The amount of label on the solid phase is a function of the amount of analyte in the sample.
The homogeneous assay configurations do not require the separation of the test solution and the indicator reagent prior to the detection of the indicator reagent or binding complexes. This broad classification includes many formats such as agglutination and precipitation assays as well as others known to those skilled in the art for the detection of analytes. Both direct and indirect agglutination assays can be performed.
It will be appreciated by those skilled in the art that the selection of any given label, binding member, ancillary binding member or solid phase material is generally not critical to the present invention. The materials are chosen to optimize the results provided by the chosen assay configuration.
The methods of the present invention can also be carried out using competitive assay formats. In a solid phase competitive assay, the capture reagent again typically involves a specific binding member which has been affixed to a solid phase material and which is contacted with both test sample and an indicator reagent. The indicator reagent, however, can be formed from an analyte or analyte-analog which has been conjugated with a label. A binding reaction occurs and results in the formation of complexes of (1) immobilized capture reagent/analyte complex and (2) immobilized capture reagent/indicator reagent complex. Alternatively, the immobilized specific binding member can be an analyte or analyte-analog with which the test sample analyte competes for binding to the indicator reagent. In the competitive assay, the amount of label on the solid phase is inversely related to the amount of analyte in the sample. Thus, a positive test sample will generate a decrease in signal.
In the present invention, a solid phase sandwich assay is used to detect the presence or amount of anti-polymer antibodies in body fluid. Typically, the capture reagent is polymer antigen, or individual subunits thereof, immobilized upon a solid phase material. After the antigen is affixed to the solid phase material, the body fluid sample is incubated with the capture reagent for a period of time and under conditions sufficient for the formation of specific complexes between anti-polymer antibodies in the body fluid and the polymer antigen. The solid phase material can then be washed with a buffer solution to remove unbound test sample. The buffer solution can be any buffer conventionally known and used by those skilled in the art. The resultant complexes are then incubated with an indicator reagent, such as a second labeled polymer antigen, for a period of time and under conditions sufficient for the formation of a ternary complex. The unreacted indicator reagent is then removed by again washing the solid phase with a buffer solution. The quantity of indicator reagent bound to the solid phase is then measured by a technique compatible with the label component of the indicator reagent. If quantitated, the amount of indicator reagent bound to the solid phase is proportional to the quantity of body fluid anti-polymer antibody bound to the solid phase.
In addition to nitrocellulose, we have successfully used polyvinylidene diflouride (PVDF) and nylon as alternative membrane sources in the APA line blot assay as well as adapting the assay to a standard 96-well polystyrene enzyme linked immunosorbent assay (ELISA) format. Although the APA line blot is described in detail in this patent request and was found to be the most useful, the APA line blot should be amenable to adaptation to other immunological assays including latex agglutination, antibody capture assays, radioimmunoprecipitation assays (RIPA), polystyrene bead based enzyme immunoassays (EIA), and particle concentration fluorescence immunoassays (PCFIA).
By observing the results of anti-polymer antibody assays, an accurate diagnosis or differentiation between undifferentiated rheumatic diseases and SRD provides a means to predict the immediate future course of the disease. In the present invention, the results of the assays used to detect polymer antigens and antibodies are interpreted as described below.
Test results for assays detecting the presence or amount of anti-polymer antibody in a test sample.
The results of the anti-polymer antibody (APA) test are interpreted as follows. If:
(1) said patient has no polymeric implant, then the presence of said antibody indicates that the patient has a condition predisposing to SRD;
(2) said patient has a polymeric implant, then the presence of said antibody indicates that the patient has SRD;
(3) said patient has a polymeric implant, then the absence of said antibody indicates that the patient does not have SRD;
(4) said patient has a polymeric implant and has been previously diagnosed as having undifferentiated rheumatoid disease selected from the group consisting of SRD, atypical connective tissue disease, atypical rheumatic syndrome, nonspecific autoimmune condition, or overt autoimmune diseases (such as CREST), then the presence of said antibody indicates said rheumatoid disease is SRD.
(5) said patient has no polymeric implant and has previously been diagnosed as having an undifferentiated rheumatoid disease selected from the group consisting of SRD, atypical connective tissue disease, atypical rheumatic syndrome, nonspecific autoimmune condition, or overt autoimmune diseases (such as CREST), then the absence of said antibody indicates said rheumatoid disease is predisposing to SRD.
The exemplary assays of the present invention typically involve the addition and incubation of several different reagents. A variety of different buffer and washing solutions can be used to stabilize the reagents and to remove excess reagents or test sample from the reaction. As is well-known to those skilled in the art, modifications can be made in the buffer and washing solutions, as well as in the reaction times.
The assay reagents can also be provided in kit form. A test kit to detect anti-polymer antibody would typically contain a solid phase material upon which polymer antigen is immobilized and optionally include an appropriate supply of a suitable indicator reagent, buffers and washing solutions. A test kit to detect polymer antigen would typically contain a solid phase material upon which anti-polymer antibody is immobilized or upon which components of the patient's test sample can be immobilized (e.g., direct immobilization of the antigen upon the solid phase), and optionally include appropriate amounts of a suitable indicator reagent, buffers and washing solutions. Other components such as stabilizers and preservative agents can also be present in the kit and/or in the reagents.
Methods generally known to those skilled in the immunological arts are described in Antibodies:. A Laboratory Manual by Ed Harlow and David Lane (1988). Cold Spring Harbor Laboratory. Chapters 12 and 14 of this book are hereby incorporated by reference.
The following examples describe, in detail, preferred assays according to the present invention. The examples are provided to further illustrate the advantages of the present invention and the specific experiments performed.
Materials and Methods
Sample Collection
Serum from each subject or control were collected and stored at -20� C. under the supervision of Dr. Luis Espinoza, Dr. David Burns or Dr. Oscar Gluck until shipment on ice by overnight carrier. Samples were stored at -20� C. or 4� C. until time of testing.
Anti-Polymer Antibody (APA) Line Blot Analysis
Partially polymerized acrylamide (PPA) was prepared by mixing 2.5 ml Acryl:Bis (37.5:1), 8.5 ml H2 O and 3.5 ml of 1.5M Tris. This 5% acrylamide solution was cross-linked with 100 μl of 0.01% ammonium persulfate and 20 μl TEMED (N,N,N'-Tetramethylethylenediamine), and allowed to solidify for 15 minutes in a 60 ml beaker. The PPA remains on top as a slightly viscous liquid.
Aliquots of polymer were sequentially diluted 5, 25, 125, 625, and 3,125 fold, applied to nitrocellulose membranes and allowed to air dry The nitrocellulose membranes were then cut into strips and incubated for 1 hour with blinded test sera diluted 1:400 in Western blot blocking buffer. Bound IgG or IgM were visualized by a series of reactions using biotinylated goat anti-human IgG or anti-human IgM immunoglobulin, avidin-conjugated horseradish peroxidase, and the enzyme substrates hydrogen peroxide and 4-chloro-1-naphthol.
Each anti-polymer antibody (APA) strip lot (28 strips) was run with a negative, weak-positive, and strong-positive control. The weak-positive control served to standardize the enzymatic developing portion of the assay. Strip lots were standardized based on reactivity of control sera which subsequently were used to assess the level of reactivity of test sera. Results were given on a scale from 0-3 with 3 being defined as ≧75% of the strong-positive control, 2 being defined as ≧25%, but <75% of the strong-positive control, 1 being defined as >10%, but <25% of the strong-positive control, and 0 being defined as <10% of the strong-positive control.
Autoantibody Westen Blot Assays
Nitrocellulose strips containing electrophoretically separated and transferred human epithelial cells (HEp-2) proteins were incubated with blinded subject and control sera at a concentration of 1:100 for 1 hour. Bound immunoglobulin were visualized by a series of reactions using alkaline phosphatase conjugated goat anti-human IgG, and the enzyme substrates tetra nitroblue tetrazolium chloride and 5-bromo-4-chloro-3-indlyl phosphate in aqueous dimethylformamide.
Statistical Analysis
Statistical analysis of the accumulated data was performed using StatView (Brainpower, Inc. Calabasan, Calif.) or Epilnfo software (Ludwig Cancer Institute, Sao Paulo, Brazil) and interpreted by Dr. Patricia L. Ryder, M.D., M.P.H., Tulane University, School of Public Health and Tropical Medicine.
F'ab digest
F'ab digestion was performed using a commercial F'ab digestion kit (Pierce Inc.) according to manufacturer instructions and utilized immobilized papain and protein A column purification.
Total immunoglobulin concentration immunodiffusion assay
Total IgG, IgA, and IgM was determined using a commercial immunodiffusion assay according to manufacturer instructions (The Binding Site Limited, Birmingham, England). Total IgG, IgA or IgM was determined by adding 5 ml of patient or control sera to wells in agar containing isotype-specific anti-human antibodies. After 48 hours zones of precipitation were measured and total immunoglobulin isotype concentration calculated from a standard curve.
The bis-acrylamide to acrylamide ratio was varied from 1:5 up to 1:40 in increments of 5. Mixtures with a ratio of 1:20 bis-acrylamide:acrylamide or greater bound anti-polymer antibody from a highly positive sample, and did not bind anti-polymer antibody from a negative sample. The most specific binding of anti-polymer antibody was obtained with a ratio of 1:37, which is the ratio of the monomers provided in the stock acrylamide obtained from the manufacturer. This ratio was used in all experiments described below.
The detection of anti-polymer antibodies (APAs) on the HIV-1 Western blot.
Evidence suggesting that silicone-containing medical devices induce autoimmune conditions is currently the subject of an active controversy in the biotechnology industry (Angell, 1992; Touchette, 1992). It is clear that some recipients of breast implants or other silicone-containing medical devices do experience complications, but the basis for this condition is not known. There is conflicting evidence as to whether silicone can elicit any immune response (Angell, 1992; Touchette, 1992). It was hypothesized that patients experiencing complications related to silicone gel filled implants may produce serum antibodies to common autoantigens recognized by patients with other autoimmune conditions in unique patterns. Using a combination of these Western blot assays, we tested sera from individuals experiencing complications associated with exposure to silicone. We found no appreciable increase in the incidence of serum antibodies reactive to known autoantigens. However, on both Western blot assays, approximately 50% of the silicone exposed individuals had serum antibodies that reacted to what appeared to be a high molecular weight protein that banded at the top of the Western blot strips. Immunological reactivity was clearly visible on these strips when assayed with sera from individuals exposed to silicone, but varied in intensity from strongly reactive to moderately reactive to non-reactive. Reactivity was not visualized when the strips were blotted with healthy blood donor sera, SLE sera or HIV strong-positive control sera.
Characterization of indeterminate results from silicone exposed individuals.
It was speculated that the indeterminate band at the top of the HIV-1 Western blot may be an artifact of the Western blot technique. This theory was tested by performing the Western blot transfer with a polyacrylamide gel that contained no protein. Sera from silicone exposed individuals that was positive for the indeterminate band reacted to a similar band on these "holistic" Western blot strips.
The unique band was determined not to be a protein, but a polymer composed of partially polymerized acrylamide (PPA). Polyacrylamide gels are formed as a result of free-radical polymerization of acrylamide monomers into long chains that are cross-linked to one another by bisacrylamide, as shown below. ##STR1##
This process and the final product is similar to that of silicone as shown below. ##STR2##
Compounds that can act as free-radical traps inhibit the cross-linking procedure (Bio-Rad Technical Bulletin). Oxygen present in the air is such a compound and can inhibit complete polyacrylamide cross-linking at the gel-air interface. This results in the formation of a thin layer of PPA at the air-gel interface. The PPA is electrophoretically transferred to the nitrocellulose, along with proteins in the gel, upon traditional Western blot transfer.
It was possible that PPA resulted from impurities in certain sources of the acrylamide or varied in reactivity based on the nature of cross-linker molecule employed in acrylamide polymerization (usually bisacrylamide). To test this, PPA was prepared with several sources of acrylamide and with several alternative cross-linker molecules, including acrylamide (Bio-Rad), diallyltartardiamide (Sigma), bisacrylamide (Sigma), acrylamide (Sigma), diacryloylpiperazine (Sigma), and acrylamide/bisacrylamide pre-mix (Bio-Rad). Using an APA line blot assay, both lgG and IgM reactivity to these different PPA products was determined. The reactivity of sera moderately reactive or strongly reactive for PPA did not vary appreciably to different acrylamide sources. However, IgG and IgM reactivity did vary with respect to the specific cross-linker molecule used. In the IgG-APA line blot assay, serum moderately reactive to PPA reacted with diallyltartardiamide (Sigma), bisacrylamide (Sigma) and diacryloylpiperazine (Sigma), and serum strongly reactive to PPA reacted with all six different PPA products, with especially strong reactions to PPA products including acrylamide (Sigma), diacryloylpiperazine (Sigma), and acrylamide bisacrylamide premix (Bio-Rad). Additionally, nonspecific reactivity was observed with partially polymerized polymers made only with bisacrylamide (PPB), as all serum samples, including samples strongly reactive, moderately reactive and negatively reactive to PPA showed a reaction with bisacrylamide (Sigma) in both the IgG-APA line blot assay and the IgM-APA line blot assay.
Degradation of PPB and Optimization of APA-PPB Reactivity
The nonspecific reactivity of partially polymerized bisacrylamide (PPB) demonstrated varied considerably with time and was suspected to be a result of degradation. This hypothesis was tested by making a series of line blot strips containing sera moderately reactive to PPB that had been allowed to sit at room temperature for 0 (day 0), 1 (day 1) and 2 days (day 2). PPB appeared to degrade by the second day (day 2) of sitting at room temperature, as the line blots indicated that the serum samples reacted with PPB on day 0 and day 1, but showed no reaction on day 2. However, a white precipitate was noted in the bottom of the PPB mixture that when resuspended, restored PPB reactivity. This restoration of PPB reactivity was demonstrated when on day 2, following resuspension of the PPB, the line blot indicated that the serum sample reacted with PPB. It was concluded that PPB was not degrading but had continued to polymerize, eventually precipitating out of solution. This explained the granular appearance of PPB in comparison to PPA.
To further characterize PPB, reactivity of PPB with strongly reactive sera was assessed by preparing APA line blots with several dilutions of PPB and assessing the reactivity of these strips with positive sera. The PPB dilutions tested included 1:1, 1:5, 1:10, and 1:20. Undiluted and 5 fold diluted PPB were found to be the most useful concentrations.
Development of the antipolymer antibody (APA) line blot.
A diagnostic test capable of assessing an immunological response to silicone would be useful given the controversy surrounding silicone gel filled breast implants. Therefore, an APA line blot was developed that had increased specificity and sensitivity in detecting APAs. Sera from silicone exposed and non-silicone exposed individuals was tested at primary antibody concentrations of 1:100, 1:200, and 1:400 for reactivity to PPA on APA line blots. PPA dilutions of 1:20, 1:100, 1:500, and 1:2500 were used.
The results were as follows:
(1) PPA strongly reactive (APA positive) sera from silicone-exposed individuals visibly reacted with all dilutions of PPA at all three primary antibody concentrations.
(2) PPA negatively reactive sera (APA negative) from silicone-exposed individuals was nonreactive at the three primary antibody concentrations.
(3) PPA positively reactive sera (APA positive) from non-silicone-exposed individuals was reactive at primary antibody concentrations of 1:100 and 1:200 but not 1:400.
(4) PPA negatively reactive sera (APA negative) from non-silicone exposed individuals was nonreactive at all three primary antibody concentrations.
Based on these observations, the current APA line blot assay was developed. PPA in 5, 25, 125, 625, and 3,125 fold dilutions and PPB in 0 and 5 fold dilutions were line blotted onto nitrocellulose membranes. Assays were performed using PPA strongly positive sera, moderately reactive sera, and negatively reactive sera. The assays demonstrated that at PPA dilutions of 1:5 and 1:25, strongly positive sera and moderately reactive sera showed a reaction, indicating the presence of antipolymer antibodies. Strongly positive sera also reacted at PPA dilutions of 1:125 and slightly reacted at 1:625. Negatively reactive sera showed no reaction at any of the PPA dilutions. For the undiluted PPB, the results were inconclusive as strongly positive, moderately reactive, and negatively reactive sera all showed slight reactions. No reactions were visible for the 5 fold diluted PPB.
Characterization of APAs
It was possible that APA reactivity was directly a function of total immunoglobulin concentration and not the result of specific anti-PPA serum antibodies. To determine if a correlation existed between APAs and total immunoglobulin concentration, total IgG, IgA and IgM immunodiffusion concentration assays were performed (The Binding Site Limited, Birmingham, England) on sera with varying APA reactivity. Total IgG, IgM, and IgA immunoglobulin concentration in mg/L was determined and categorized by isotype according to APA reactivity, including APA strongly reactive (APA+), APA moderately reactive (APA�), and APA negatively reactive (APA-). No correlation was found to exist between the total serum immunoglobulin of any isotype and the level of APA reactivity.
It was also possible that the anti-PPA reactivity of APAs results from non-specific interactions, as sticky antibodies are known to react with many antigens in a non-specific manner not mediated by the F'ab binding domain of the antibody. To establish the nature of APA reactivity, an APA line blot assay was performed. Two PPA strongly-reactive serum samples were digested with immobilized papain into F'c and F'ab subunits (Pierce Laboratories).
Digested APA F'ab fragments were purified by protein-A column chromatography to remove F'c fragments. The remaining PPA reactivity was assessed on APA line blots using anti-F'ab secondary antibody. Undigested strongly reactive sera, non-protein A purified F'ab digested strongly reactive sera, and F'ab containing 1.5 ml elution fractions after F'c fragment removal with protein A chromatography were compared. PPA dilutions of 1:5, 1:25, 1:125, 1:625, and 1:3125, undiluted PPB, and PPB diluted 5 fold were used in the assay.
The results showed that some PPA reactivity was lost as a result of papain digestion, as undigested strongly reactive sera reacted at all PPA concentrations, as well as in undiluted PPB, compared to non-protein A purified, F'ab digested sera, which only showed a reaction at PPA concentrations of 1:5 and 1:25, and slight reactivity at 1:125. However, subsequent to F'c fragment removal with protein A column chromatography, the remaining PPA reactivity appeared to reside predominantly in F'ab purified fractions.
Frequency of APAs in individuals exposed to silicone breast implants.
Exposure to silicone breast implants can result in the manifestation of symptoms and complications that collectively are dissimilar from previously recognized or defined rheumatological diseases and therefore will be uniquely identifiable with the appropriate diagnostic tests. Using a combination of APA line blot techniques, it was determined that the approximately 50% (363/667) of persons reporting complications following silicone breast implantation produced APAs serum antibodies. This was significantly greater than the 7% (7/100) observed in healthy blood donor sera (p<0.0005). Sera from patients experiencing other autoimmune complications (SLE, RA, juvenile rheumatoid arthritis, or diffuse scleroderma) demonstrated APA antibodies in less than 10% of the cases. Therefore, anti-polymer antibodies do not seem to be a general marker for autoimmunity. However, patients with the CREST form of scleroderma demonstrated detectable APAs in 50% (10/20) of the cases tested. This is of interest because scleroderma-like symptoms, including tightness of skin, contracture, sclerodactyly, alopecia, edema, telangiectasias, rash, and changes in pigmentation, have frequently been associated with silicone breast implants (Brozena et al., 1988; Vasey et al., 1991; Spiera et al., 1994).
TABLE 1______________________________________Anti polymer antibodies (APAs) in recipients of silicone breastimplants detectable by Line immunoblotting. # positive PercentDonor Group/Diagnosis /# tested positive Significance______________________________________healthy blood donors 9/100 9.0%silicone implant recipients 363/667 50.7% p < 0.0005aScleroderma (CREST) 10/20 50.0% p < 0.0005Scleroderma (diffuse) 1/10 10.0% NSSbsystemic lupus erythematosus 13/205 6.3% NSSadult rheumatoid arthritis 3/92 3.3% NSSjuvenile rheumatoid arthritis 1/11 9% NSS______________________________________ a student test b NSS = not statistically significant
Correlation of rheumatic symptoms with production of antibodies to PPA.
Patients with complications associated with exposure to silicone from breast implants were 17 times more likely to produce detectable APAs than healthy blood donors (95% confidence limit 7.55-46.69). This percentage is highly relevant to complications from breast implants because not all silicone breast implant recipients who are currently seeking treatment actually are experiencing complications directly resulting from silicone exposure.
To correlate the anti-polymer antibody assay with the occurrence of specific clinical symptoms, sixty-nine patients with silicone disease as defined by joint aching about the MP's, PIP's, dysesthsias, paresthesias, multiple tender spots including the occupant, upper cervical, epicondyler, hips, knees and ankles, overwhelming fatigue, general malaise and widespread pain were studied. Of the 69 patients, 58 (84.06%) were felt to have silicone disease and 11 (15.94%) were felt to have no disease or localized myofascial discomfort.
Of the 69 patients, 17 patients had other antibodies and may or may not have silicone disease. Of these, 5 patients had well-known rheumatic disease by American College of Rheumatology criteria, including 2 patients with primary Sjogren's syndrome, 1 patient with CREST, 1 patient with seropositive rheumatoid arthritis and 1 patient who met ACR criteria for lupus. There was 1 patient with chronic persistent hepatitis. Four patients had positive rheumatoid factors and 7 patients had anti-thyroid antibodies.
Fifty-eight patients had silicone disease. Of these 58, 38 (65.52%) had a negative antinuclear antibody (ANA) test result, while 20 (34.48%) had a positive ANA result. Eleven patients had no silicone disease. Of the 11, six patients (54.55%) had a negative ANA result, while 5 (45.45%) had a positive result.
Thirty-five out of the 58 patients that had silicone disease tested positive for silicone antibodies, including 22 patients (37.93%) who clearly had the antibodies and 13 (22.41%) who had probable silicone antibodies. The remaining 23 patients (39.66%) with silicone disease had no silicone antibodies.
Thus, roughly sixty percent of the patients with silicone disease had the silicone antibody.
Of the remaining 11 patients without any silicone disease, only 4 patients had a silicone antibody. Seven of the 11 (63.64%) who did not have silicone disease had no silicone antibody. This antibody is a very good predictor of silicone disease since 60% of patients with disease had the antibody.
The antinuclear antibody test was present at a low titer in 20 patients with disease, making it likely to be present in about a third of the patients with silicone disease. Those who had no disease and localized myofascial pain had about 40% antinuclear positive antibodies, making the antinuclear antibody test not a good predictor of silicone disease.
The following tables (Tables 2-4) demonstrate the use of the anti-polymer antibody assay in an ELISA format. The dilution ratio of the antigen, partially polymerized polyacrylamide, attached to each well of a polystyrene 96-well plate is shown in column 1 (left hand column). The serum dilution ratio (1/50, 1/100, etc.) for representative patient samples is shown in the first row at the top of each column. Strong-positive, weak-positive, and negative reacting serum samples were tested. The serum was incubated in the wells containing the antigen, then reacted with a goat-anti-human alkaline phosphatase labelled secondary antibody. The data are presented as the optical density from the signal production system consisting of the reaction of this labelled secondary antibody with the substrate 5-bromo-4-chloro-3-indole phosphate (BCIP) phosphate. Wells containing neither PPA nor serum in the column marked blank are set to zero relative to the other wells.
TABLE 2______________________________________STRONG POSITIVE Serum DilutionPPA Dilution 1/50 1/100 1/200 1/400______________________________________0 0.392 0.068 -0.042 -0.091/15625 0.73 0.583 0.378 0.3641/3125 2.013 2.5 2.038 1.5871/625 2.5 2.5 2.5 2.51/125 2.5 2.5 2.5 2.0471/25 2.5 2.5 2.5 2.51/5 2.5 2.5 2.5 1.3731/ 2.5 2.5 2.5 2.5______________________________________
TABLE 3______________________________________WEAK POSITIVE Serum DilutionPPA Dilution 1/50 1/100 1/200 1/400______________________________________0 0.155 0.075 -0.038 -0.11/15625 0.435 0.18 0.105 -0.081/3125 1.404 0.91 0.428 0.1351/625 2.062 1.536 0.735 0.341/125 2.5 2.5 1.254 0.3751/25 2.5 1.896 1.061 0.4951/5 2.5 2.5 1.45 0.6681/ 2.5 2.5 2.5 1.379______________________________________
TABLE 4______________________________________NEGATIVE Serum DilutionPPA Dilution 1/50 1/200 1/400 blank______________________________________0 0.117 -0.062 0 01/15625 0.366 -0.1 0.02 01/3125 0.006 -0.012 0.006 01/625 0.106 -0.045 0.055 -0.11/125 0.01 -0.098 0.008 -0.11/25 0.047 0.097 -0.1 0.2241/5 -0.004 -0.087 0.072 -0.11/ -0.039 -0.1 -0.1 -0.1______________________________________
The detection of APAs in this study may represent immunology cross-reactivity directed against silicone or another component found in breast implants. Alternatively, silicone may function as an adjuvant and/or physically interact with cellular components present in the surrounding connective tissue, such as collagen. This may result in the structural alteration of the silicone or the cellular component so as to antigenically resemble PPA. Silicone, collagen, and PPA are cross-linked polymers. It is possible that any antigenic relationship among these substances results from the type and degree of cross-linking, and not from chemical composition of the polymer.
The observation that exposure to silicone implants does not appear to be necessary for the development of APAs is consistent with this latter hypothesis. About 7% of the healthy population appear to produce antibody that cross-react with PPA. This must be qualified because silicone-containing devices are widely used in medicine, commerce, and industry, and it is possible that our normal blood donors may have been unknowingly exposed to silicone. Alternatively, individuals with pre-existing APAs may be predisposed to complications following silicone implantation, although this has yet to be established. Current attempts are being made to establish the correlation of APAs titer to silicone breast implant complication severity and symptomatology.
Based on the observations with PPA and PPB, it is suspected that APAs react with a heterogeneous polymeric structure (possibly in a circular conformation) composed of acrylamide/bisacrylamide that may antigenically resemble a silicone implant polymer component. Although conjecture, a circular structure may provide the level of complexity necessary to convey antigenicity to a relatively simple polymer structure. Additionally, circular polymer complexes would be resistant to further polymerization and therefore, be more likely present as a partially polymerized component of an acrylamide gel.
The identification of a newly described anti-polymer antibody (APA) that may be associated with silicone related complications was also detailed in this dissertation and was first detected with the HIV-1 Western blot. This led to the partial characterization of the antigen as a polymer of partially polymerized acrylamide (PPA) with specific composition. APAs that react with PPA were shown to be specific, of high titer, independent of total immunoglobulin concentration, and predominantly found in patients with complications related to silicone exposure. Based on these observations, a preliminary diagnostic assay has been developed. Currently, the correlation between seroreactivity on this assay and silicone related autoimmune symptomatology is being assessed.
Although the controversy concerning the relationship between silicone gel filled breast implants and the development of autoimmune disease is not resolved (Gabriel et al., 1994), the results obtained using the anti-polymer antibody line blot assay make a compelling argument that at least some individuals mount a specific anti-polymer immune response subsequent to silicone exposure.
The identification and characterization of non-viral antigens present on the HIV-1 Western blot should help in the interpretation of indeterminate results obtained on the assay. Given that any reactivity on the HIV-1 Western blot assay is considered an indeterminate result regarding a person of uncertain HIV serostatus, the ramifications of reactivity in blood donors are important. The nature of the interplay between viral proteins, cellular proteins and other antigens may provide information relevant to the understanding of mechanisms leading to systemic autoimmune diseases.
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|Cited Patent
|Filing date
|Publication date
|Jan 28, 1981
|Jan 24, 1984
|Grumman Aerospace Corporation
|Multiprocessor with staggered processing
|Oct 30, 1991
|May 17, 1994
|Ribi Hans O
|Polymeric immunological adjuvants
|Dauber, J. H., Rossman, M. D., Pietra, G. G., Jimenez, S. A., Daniele, R. P. Experimental silicosis. American Journal of Pathology, 1980; 101: 595 607 and FIGS. 1 5.
|Dauber, J. H., Rossman, M. D., Pietra, G. G., Jimenez, S. A., Daniele, R. P. Experimental silicosis. American Journal of Pathology, 1980; 101: 595-607 and FIGS. 1-5.
|Kossovsky et al., Arch Pathol lab Med. 118, pp. 686 693 (1994) Silicone Breast Implant Pathology .
|Kossovsky et al., Arch Pathol lab Med. 118, pp. 686-693 (1994) "Silicone Breast Implant Pathology".
|Kossovsky, N. et al: Surface dependent antigens identified by high binding avidity of serum antibodies in a subpopulation of patients with breast prostheses. Journal of Applied Biomaterials 1993; 4: 281 288.
|Kossovsky, N. et al: Surface dependent antigens identified by high binding avidity of serum antibodies in a subpopulation of patients with breast prostheses. Journal of Applied Biomaterials 1993; 4: 281-288.
|Lilla, J. A., and Vistnes, L. M.: Long term study of reactions to various silicone breast implants in rabbits. Plast & Reconstr. Surg. 1976; 57: 637 649.
|Lilla, J. A., and Vistnes, L. M.: Long-term study of reactions to various silicone breast implants in rabbits. Plast & Reconstr. Surg. 1976; 57: 637-649.
|Naim, J. O., Lanzafame, R. J. and van Oss, C. J: Immuno logical adjuvancy of silicone gel Immunological Investigations 1993; 22: 151 161.
|Naim, J. O., Lanzafame, R. J. and van Oss, C. J: Immuno-logical adjuvancy of silicone-gel Immunological Investigations 1993; 22: 151-161.
|Nalbandian, R. M., Swanson, A. B., Maupin, B. K.: Long term silicone implant arthroplasty. Journal of the American Medical Assn. 1983; 250: 1195 1200.
|Nalbandian, R. M., Swanson, A. B., Maupin, B. K.: Long-term silicone implant arthroplasty. Journal of the American Medical Assn. 1983; 250: 1195-1200.
|Nosanchuk, J.S.: Injected dimethylpolysiloxane fluid: A study of antibody and histologic response, Plast. & Reconstr. Surg. 1968; 42: 562 566.
|Nosanchuk, J.S.: Injected dimethylpolysiloxane fluid: A study of antibody and histologic response, Plast. & Reconstr. Surg. 1968; 42: 562-566.
|Picha, G. J. and Goldstein, J.A.: Cellular response to silicone. Plast. & Reconstr. Surg. 1991; 87: 490 500.
|Picha, G. J. and Goldstein, J.A.: Cellular response to silicone. Plast. & Reconstr. Surg. 1991; 87: 490-500.
|Tenenbaum et al., Arthritis and Rheumatism, 36 (9 Suppl), Abstract S118 (1993) "Identification of a novel antigen recognized by silcone implant recipients".
|Tenenbaum et al., Arthritis and Rheumatism, 36 (9 Suppl), Abstract S118 (1993) Identification of a novel antigen recognized by silcone implant recipients .
|Tenenbaum, S. A., Silveira, L. H., Martinez Osuna, P., Cuellar, M. L., Garry, R. F. and Espinoza, L. R.: Identification of a novel autoantigen recognized in silicone associated connective tissue disease. American College of Rheumatology 1992.
|Tenenbaum, S. A., Silveira, L. H., Martinez-Osuna, P., Cuellar, M. L., Garry, R. F. and Espinoza, L. R.: Identification of a novel autoantigen recognized in silicone-associated connective tissue disease. American College of Rheumatology 1992.
|Teuber et al., Journal of Autoimmunity, 6, pp. 367 377 (1993) Anti collagen Autoantibodies are Found in Women with Silicone Breast Implants .
|Teuber et al., Journal of Autoimmunity, 6, pp. 367-377 (1993) "Anti-collagen Autoantibodies are Found in Women with Silicone Breast Implants".
|Wolf, L. E., Lappe, M. Peterson, R. D. and Ezrailson, E. G.: Human immune response to polydimethylsiloxane (silicone): screening studies in a breast implant population. The FASEB Journal 1993; 7:1265 1268.
|Wolf, L. E., Lappe, M. Peterson, R. D. and Ezrailson, E. G.: Human immune response to polydimethylsiloxane (silicone): screening studies in a breast implant population. The FASEB Journal 1993; 7:1265-1268.
|Citing Patent
|Filing date
|Publication date
|Sep 23, 1999
|Apr 6, 2000
|Quest Diagnostics Investments Incorporated
|Biological assay compositions containing non-interfering, foam-inhibiting and foam-collapsing agents
|U.S. Classification
|435/7.9, 436/506, 435/7.94, 435/975, 435/7.95, 435/7.1, 436/518, 436/72, 436/509, 436/811, 436/501, 435/7.92
|International Classification
|Cooperative Classification
|European Classification
|Oct 5, 1994
Owner name: ADMINISTRATORS OF THE TULANE EDUCATIONAL FUND, LOU
Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:GURRRY, ROBERT F;TENENBAUM, SCOTT A.;PLYMALE, DOUGLAS A.;REEL/FRAME:007468/0088
Effective date: 19941005
|Oct 13, 2000
|Fee payment
Year of fee payment: 4
|Oct 13, 2004
|Fee payment
Year of fee payment: 8
|Oct 6, 2008
|Fee payment
Year of fee payment: 12


text:
Times reporter Joshua Mayers' rankings run Wednesdays during the regular season.
|Joshua Mayers' MLS power rankings
|Rankings will run Wednesdays during the regular season
|Team (prev. rank)
|1. San Jose (1)
|Already clinched a 2013-14 CCL berth and could lock up the Supporters' Shield next.
|2. Sporting K.C. (2)
|Will miss Roger Espinoza for 2-4 weeks as the midfielder recovers from an ankle sprain.
|3. Real Salt Lake (5)
|Road win in L.A. has the team closing on a coveted top-three seed in the Western Conf. playoffs.
|4. Sounders FC (7)
|Defense produced shutouts in consecutive weeks versus rivals Vancouver and Portland.
|5. Chicago (3)
|Became the second team in the East to lock up a playoff spot with a 2-0 road win in New York.
|6. N.Y. Red Bulls (4)
|Can they overcome the stunning midseason removal of GM Erik Soler and make the playoffs?
|7. L.A. Galaxy (6)
|A knee injury to Landon Donovan will keep him out of World Cup qualifiers this month.
|8. D.C. United (9)
|No team has been better than Ben Olsen's in the past five games, with four wins and a tie.
|9. Houston (8)
|Second-year forward Will Bruin is up to 12 goals, tied for 10th-best in MLS.
|10. Columbus (11)
|GK Andy Gruenebaum, a former supplemental draft pick, leads the league with 117 saves.
|11. Vancouver (13)
|Can clinch the final playoff spot in the West with a win next weekend or a Dallas loss.
|12. FC Dallas (10)
|Blew a lead to lowly Chivas USA, which was a devastating blow to its postseason hopes.
|13. Montreal (12)
|Ex-Sounder Sanna Nyassi scored his sixth goal, a new career high, in a 1-1 tie vs. Houston.
|14. Philadelphia (16)
|Three wins in four games has the team .500 since a midseason coaching change (8-8-4).
|15. Colorado (14)
|Eight goals from Omar Cummings and Conor Casey in 44 combined games isn't nearly enough.
|16. Portland (15)
|Will get one last chance to clinch the Cascadia Cup, but needs a win in Vancouver on Oct. 21.
|17. New England (17)
|There are rumblings of potential moving games to a new venue. Would that provide a spark?
|18. Chivas USA (18)
|22 goals are 10 fewer than the next worst team (Portland), five fewer than SJ's Wondolowski.
|19. Toronto FC (19)
|Hasn't won a game since July 18. It's just about time to start scouting for that No. 1 draft pick.


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You are a fan of throttlebodies under ? Come to discover the best forums throttlebodies under on the internet and share your experience with a community fan of throttlebodies under . You can also build a forum throttlebodies under and create your online discussion.
Car Talk for Car People, Mad about Performance and BHP! !
free, forum, massive, power, extreme, peugeot, renault, citroen, nissan, toyota, ford, vauxhaull, drag, racing, track, handling, turbo, supercharger, fast, quick, #throttlebodies, cams, tuning, mitsubishi, subaru, skyline, drifting, supra


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The press release for Red Hat Enterprise Linux 5.3 can be found at BusinessWire.com.
Michael Larabel is the principal author of Phoronix.com and founded the site in 2004 with a focus on enriching the Linux hardware experience. Michael has written more than 10,000 articles covering the state of Linux hardware support, Linux performance, graphics drivers, and other topics. Michael is also the lead developer of the Phoronix Test Suite, Phoromatic, and OpenBenchmarking.org automated benchmarking software. He can be followed via Twitter or contacted via MichaelLarabel.com.


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Baywatch Resort - Goa (state)
A health club, a restaurant and free self parking are featured at this resort. Escape the stress of everyday life at Lifestyle Spa, offering facials and body scrubs, as well as Ayurvedic treatments, body wraps and body treatments. Relax in the outdoor pool and enjoy the free pool cabanas. In addition to the on-site spa, leisure facilities on offer include a sauna. High-speed (wired) Internet access is available.
Baywatch Resort - Goa (state)
Hotel Info: 1-877-214-4288from $44
- Suite, 1 King Bed
- Deluxe Room, 1 Double Bed
Also popular with travelers from the USA
At a glance
Key facts
Hotel size
- This hotel has 90 rooms
- This hotel is arranged over 2 floors
- Check-in time starts at 3 PM
- Check-out time is 11 AM
Required at check in
- Credit card or cash deposit required
- Government-issued photo ID required
- Minimum check-in age is 18
Travelling with others
- No pets or service animals allowed
Extra people
- Roll-away beds available, charges may apply*
- WiFi and wired Internet access in public areas *
- WiFi in rooms *
- Free self parking
In the hotel
- Restaurant
- Outdoor pool
- Free pool cabanas
- Health club
- Tennis on site
- Full-service spa
- Spa treatment room(s)
- Parasailing nearby
- Scooter/moped rentals nearby
- Pool umbrellas
- Steam room
- Sauna
- Billiards or pool table
- One meeting room
- 24-hour front desk
- Dry cleaning/laundry service
- Laundry facilities
- Luggage storage
- Wedding services
- Elevator/lift
In the room
- In-room climate control (air conditioning)
- Air conditioning
- Ceiling fan
- Minibar
- Coffee/tea maker
- Blackout drapes/curtains
- Balcony
- Private bathroom
- Bathtub only
- Free toiletries
- Hair dryer
- 32-inch TV
- Premium TV channels
- Desk
- WiFi (surcharge)
- Phone
- Free bottled water
- Daily housekeeping
- In-room safe
- Connecting/adjoining rooms available
Special features
Lifestyle Spa has 4 treatment rooms including rooms for couples. Services include facials, body wraps, body scrubs, and body treatments. A variety of treatment therapies are provided, including aromatherapy and Ayurvedic. The spa is equipped with a sauna.
Guests under 12 years old are not allowed in the spa.
Baywatch Resort - Goa (state)'s small print
The property has connecting/adjoining rooms, which are subject to availability and can be requested by contacting the property using the number on the booking confirmation.
Only registered guests are allowed in the guestrooms.
Guests under 12 years old are not allowed in the spa.
Reservations are required for massage services and spa treatments and can be made by contacting the property before arrival at the number on the booking confirmation.
Mandatory fees
You'll be asked to pay the following charges at check in or check out:
- Christmas Day (25 December) Gala Dinner per adult: INR 4598.00
- Christmas Day (25 December) Gala Dinner per child: INR 1875 (from 5 to 11 years old)
- New Year's Eve (31 December) Gala Dinner per adult: INR 4500.00
- New Year's Eve (31 December) Gala Dinner per child: INR 2250 (from 5 to 11 years old)
- Valentine's Day (14 February) Gala Dinner per adult: INR 1000.00
- Valentine's Day (14 February) Gala Dinner per child: INR 500.00 (from 5 to 11 years old)
- Gala Dinner on 29 October per adult: INR 1000
Optional extras
Rollaway beds are available for INR 750 per night
Airport shuttle service is offered for an extra charge of INR 1500 per vehicle (one way)
WiFi is available in guestrooms for INR 100 for 30 minutes (rates may vary)
WiFi is available in public areas for INR 100 for 30 minutes (rates may vary)
High-speed Internet access (wired) is available in public areas for an extra charge
We have included all charges provided to us by this hotel. However, charges can vary, for example, based on length of stay or the room you book.


text:
- Differential Diagnosis
- Diseases
- Drugs
- More
- Try building your search one term at a time, and be as specific as you can! Search term example: "chronic cough".
- Do not enter multiple findings such as "anemia, chronic cough, weight loss, vomiting" all at the same time.
- After selecting your term from the search results a list of possible diagnoses will be generated. If the list is too long, you will be able to narrow it down by entering additional terms.
- Do not enter values such as "heart rhythm 110" or "sodium 125", instead use "tachycardia" or "hyponatremia".
Sign-in (or register) to check out the new features we've just launched!
Differential Diagnosis For Howell Jolly bodies/rbcs (Lab)
Available only to registered users.
- Suggest
- 13 possible diagnoses found
- Surgical, Procedure Complication
- Splenectomy
- Infected organ, Abscesses
- Hemolytic anemia of infection/acute
- Neoplastic Disorders
- Leukemia, acute
- Acute Lymphoblastic/lymphocytic leukemia ALL
- Leukemia
- Allergic, Collagen, Auto-Immune Disorders
- Hemolytic anemia, autoimmune
- Evan's syndrome (AHA/Immune TP)
- Deficiency Disorders
- Folic acid deficiency anemia
- Congenital, Developmental Disorders
- Splenic agenesis syndrome.
- Hereditary, Familial, Genetic Disorders
- Thalassemia major
- Thalassemia-hemoglobin C disease
- Reference to Organ System
- Megaloblastic anemia
- Pernicious anemia
- Synonyms
- Bodies Howell-Jolly, Howell Jolly Bodies, Howell Jolly bodies (finding), Howell Jolly body, Howell Jolly body (finding), HOWELL-JOLLY BODIES, Howell-Jolly body, Howell-Jolly body (morphologic abnormality), Lab
- Definition
- Be the first to add a definition for Howell Jolly bodies/rbcs (Lab)
- External Links Related to Howell Jolly bodies/rbcs (Lab)
- Wikipedia
- Merck
- Images
- PubMed (National Library of Medicine)
- NGC (National Guideline Clearinghouse)
- Medscape (eMedicine)
- Harrison's Online (accessmedicine)
- NEJM (The New England Journal of Medicine)


text:
Miller slammed in a 76th-minute winner, just three minutes after his introduction at London Road.
Boro had earlier seen Faris Haroun's early brace wiped out by Peterborough's on-loan striker Dwight Gayle, who struck twice in an impressive display.
"There's no doubt in my mind we deserved to win it but we have conceded three very poor goals - one from our own corner, one when we have failed to pick up a man at the back post and the third from a goalkeeping mistake."
Haroun's first came in the ninth minute when he capped off a fine counter-attack to put away Emmanuel Ledesma's pass and 11 minutes later he converted Stuart Parnaby's cross at the back post.
But Posh fought back through on-loan Gayle with a rasping effort before the break and shortly into the second half by converting Michael Bostwick's header, before Miller's strike.
- Sports & Recreation
- Soccer
- Faris Haroun


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Trending This Week (Aug 29)
- August 28, 2014
Every Friday we pull our favorite links from across the inter-webs. This week's trending links include a look at mutli-ethnic churches responding to racial injustice, lots of tips for structure, campus ministry, reconnecting with students, and plenty of fuel for your procrastination.
Blogs From YouthSpecialties.com This Week
Les Christie shares some great thoughts on caring for the students that are the most difficult to love: "Caustic Kids" –Â CLICK TO VIEW
Stephanie Caro (@StephanieCaro) joined us last week for an incredible Google Hangout on Small Church Youth Ministry, and here's the video –Â CLICK TO VIEW
The NNYM and YS have teamed up for the National Youth Ministry Networking Day on Oct 16th! Here are most of the details  – CLICK TO VIEW
Blogs From Other Great Youth Workers This Week
Time posted a fascinating article on responses from multi-ethnic churches on racial injustice: "Multi-Ethnic Churches Lament America's Racial Injustice" Â –Â CLICK TO VIEW
Chris Mucha wrote a great post about "6 Tips for Creating Structure and Boundaries in Ministry" –Â CLICK TO VIEW
Ben Trueblood (@BenTrueblood) shared another "6 tips…" post about effective campus ministry: "6 Ways to Win on the School Campus" Â –Â CLICK TO VIEW
Andy Blanks (@AndyBlanks) wrote a great overview of different roles youth workers take: "5 Roles Youth Workers Play in the Lives of Teenagers" –Â CLICK TO VIEWÂ
AwanaYM (@AwanaYM) offered great ways to reconnect with students: "5 Tips for Reconnecting with Students" –Â CLICK TO VIEW
Fun Things To Fuel Your Procrastination
Mark Matlock's Ice Ice Baby Bucket Challenge – CLICK TO VIEW
Action movie Kid Part 2 –Â CLICK TO VIEW
A GOPRO on a high-speed jet ski in a canyon river – CLICK TO VIEWÂ
The Smell-Tasting Experiment – CLICK TO VIEW


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Pokemon Origin
View Single Post
December 26th, 2008 (8:49 AM).
What's next?
Crystal Tier
Join Date: Aug 2007
Location: The Ruins Of Alph
Age: 21
Gender: Male
Nature: Adamant
Posts: 249
Originally Posted by
Can you please put Crystal Onix in the Orange Islands and the gaint tentacruel from episode Tentacruel & Tentacool and place like Bulbasaur's Mysterious Garden if you could put things in like this i would like to help but i don't know how to use the programes (sad face)
I don't know if other people have wanted to do this but i think you should put New Island(Mewtwo's island) from pokemon movie 1, Fire Island(Moltres) to get the fire-based sphere + Lightning Island (Zapdos) to get the lightning-based sphere + Ice Island (Articuno) to get the ice-based sphere from pokemon movie 2, The mansion to battel the Crystal Pokémon of molly created by Entei from pokemon movie 3, to goto the Lake of Life (Celebi's home) from movie 4, to go to the water-themed johto city of Altomare (Latias and Latios home) from pokemon movie 5, to see the Millennium Comet, which appears in the night sky for seven days once every thousand years. It is, at the same time, when the legendary Pokémon Jirachi awakens from a long slumber to absorb the comet's energy from pokemon movie 6, to go to the place were Deoxys and Rayquaza battel from pokemon movie 7, to go to Cameron Palace where a festival is being held to celebrate Sir Aaron and enter the battle and win Aura Guardian and see Lucario and mew also to go to Tree of Beginning to battel Regirock, Regice and Registeel the tree's guardians from pokemon movie 8, to go the Temple (Manaphy's home) from pokemon movie 9, to go to the Space-Time Tower to see Palkia, Dialga and Darkrai battel from pokemon movie 10, to go to the Reverse World and see Giratina, Shaymin, Dialga and Regigigas and what ever else happens from pokemon movie 11 and the events from movie 12 if possible. I think by putting this in the game it would make it 100x better in my opinion.
Actually all those, discluding the tentacruel, are possible in RMXP. But again, they wouldn't be easy. I would have to get some requests for them.
Pokemon: Origin Version
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text:
At its annual Clark County luncheon on April 12, charity Loaves and Fishes will recognize Larry Smith with its Compassion for Seniors award.
Smith led the Vancouver-Clark Parks and Recreation Department before being elected to the Vancouver City Council in 2004. As parks and recreation director, he helped implement SNAP, a senior nutrition program. And he played a key role in introducing Loaves & Fishes to Clark County in 2006. Loaves & Fishes, the so-called "Meals on Wheels People," delivers food to homebound senior citizens.
The luncheon is set for noon Thursday, April 12, at the Hilton Vancouver Washington, 301 W. Sixth St. The event is free, but a donation appeal will be made and registration is required. Call 503-953-8114 or visit feedseniors.org.


text:
Tides of War: Magus/X Feats (PFRPG) PDF
Kineticists of Porphyra II (OGL) PDF
Rappan Athak Expansions, Volume I (PFRPG) PDF
Pathfinder Battles—Rusty Dragon Inn: Merchant
Pathfinder Battles—Rusty Dragon Inn: Cutpurse
109 posts. 3 reviews. No lists. No wishlists.
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Print Edition
I like the fact that the screen is sturdy and high. The D&D 4E screen was also sturdy, but unfortunately it was too low. I guess some DMs liked that as it allowed them to actually see the players, but I always felt a bit "unprotected" suspecting that the tall player to my left is peeking over the screen. No such problem with the Pathfinder screen!
The art of the screen is also beautiful, although it's nothing new: we've been seeing these iconic characters for several years now.
Now what I don't like about the screen is the choice of some of the tables included. Why do I really need the following two tables during a game session:
Experience Point Awards
Treasure Values per Encounter
These tables are useful before a session, when planning the encounters. I've never in my life used these tables during a game session.
I would rather have more vital tables to the actual gameplay included. I'm missing, for example, the very important table that shows which actions provoke Attack of Opportunity and which do not. Also more conditions could have been included. These were the 2 things that I felt missing after 1 game session with the screen; I'm sure there are more.
As a side note the D&D 4E screen also included the above useless tables. Pathfinder might have taken the idea from there... pity.
Print Edition
Out of print
A book about the Empire of Cheliax that doesn't contain a map of the place? Yes, there are maps of the 2 main cities (quite inconsistent in their presentation) but what about the land itself? It's as if owning the Pathfinder Campaign Setting is a prerequisite to actually making sense of this book, something which is not really written in the product's description. The other problem I had is that while it presents things in Pathfinder RPG compatible format largely, there are some inconsistencies, for example a feat that still refers to the old grappling rules. Otherwise this is a good book with some interesting bits and a very nice presentation.
Pretty good adventure, although it might be a bit tough for inexperienced GMs to run. But what's up with the proofreading? "See also heard the jabs and mockery the house staff heaped daily on her brother. Fiercely defensive, the noble girl once cut one of her first handmaids wirh a broken wine bottle". See instead of she? Wirh instead of with? And that's just one example in one paragraph. The adventure is full of such typos and mistake. Paizo, you could do better!
©2002–2016 Paizo Inc.®. Need help? Email email@example.com or call 425-250-0800 during our business hours: Monday–Friday, 10 AM–5 PM Pacific Time. View our privacy policy. Paizo Inc., Paizo, the Paizo golem logo, Pathfinder, the Pathfinder logo, Pathfinder Society, GameMastery, and Planet Stories are registered trademarks of Paizo Inc., and Pathfinder Roleplaying Game, Pathfinder Campaign Setting, Pathfinder Adventure Path, Pathfinder Adventure Card Game, Pathfinder Player Companion, Pathfinder Modules, Pathfinder Tales, Pathfinder Battles, Pathfinder Online, PaizoCon, RPG Superstar, The Golem's Got It, Titanic Games, the Titanic logo, and the Planet Stories planet logo are trademarks of Paizo Inc. Dungeons & Dragons, Dragon, Dungeon, and Polyhedron are registered trademarks of Wizards of the Coast, Inc., a subsidiary of Hasbro, Inc., and have been used by Paizo Inc. under license. Most product names are trademarks owned or used under license by the companies that publish those products; use of such names without mention of trademark status should not be construed as a challenge to such status.


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I need a good trainer workout, I'm trying to get on the trainer after riding outside for the past week. I'm looking a battenkill this year in the junior 17+18 class. The past workouts on the trainer I've been doing are 45min long. I've been doing one song(3 min) about 3/4 resistance on my new mag+ at a somewhat hard tempo and resistance, than one song (3 min) full resistance dropping 1 gear hard. I did probably 14-16 reps than a 10min cool down. I feel like I'm getting faster and stronger, i increased my average over a 50mile from 22.1 to 25.8mph after two times on the trainer. I feel like i need something different to throw into the mix. I don't have cadence or a hr monitor.
thanks - Hansel


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home > first Aid & injuries center > first Aid & injuries a-z list > wilderness bristleworm sting article > wilderness bristleworm sting topic guide
Wilderness: Bristleworm Sting Topic Guide
Bristleworm Sting: Bristleworm sting symptoms include redness, a burning sensation, pain, swelling, and rash. Treatment of bristleworm sting include removal of the spines and possibly antibiotics to prevent infection.
Scuba Diving and Snorkeling Tips Safe scuba diving and snorkeling tips include protecting marine animals while enjoying the sport, equipment care, and emergency preparedness.


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