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An approximately six-month-old puppy is now in the care of the ASPCA after being rescued from cruelty by officers of the New York City Police Department (NYPD). A concerned citizen called the NYPD early Friday morning after witnessing the puppy, named Hennessy, being beaten with a shovel and buried in the snow.
Hennessy—now called "Lacey"— is recovering in the intensive care unit of the ASPCA Animal Hospital, where she is receiving around-the-clock care and resting from her injuries. Despite the abuse she has endured in the past, Lacey is an affectionate puppy who appears to have a strong spirit.
"The amount of pain inflicted on such a young, vulnerable dog is truly inconceivable," says Howard Lawrence, Senior Director, ASPCA Anti-Cruelty Group. "Our staff is doing all we can to make her comfortable and applauds everyone involved in pursuing justice for Lacey."
The NYPD made an arrest in this case, and the alleged abuser has been charged with Aggravated Cruelty to Animals, Torturing and Injuring Animals and Criminal Possession of a Weapon in the Fourth Degree.
It is too soon for us to comment on Lacey's ultimate prognosis, and as this is an open case, we cannot provide further information at this time.
"We applaud the brave citizens who witnessed this barbaric act and called the NYPD," says Lawrence. "We encourage anyone who witnesses an animal crime in progress in New York City to please call 911 immediately. You may be saving that animal's life."
To report animal cruelty not in progress, please call 311 in New York City. If you are outside of New York City, visit our Fight Cruelty FAQs to learn how to report animal cruelty in your area.
To help save more animals like Lacey, please make a donation to the ASPCA today.
We're all still reeling from last week's revelations in The New York Times of animal mistreatment that verges on the sadistic at the USDA's U.S. Meat Animal Research Center (USMARC). The violent images depicted in the exposé—a pig being dissected alive by an apparently gleeful researcher, a young cow left to die from her injuries after USDA employees immobilized her and allowed her to be mounted by bulls for hours until her legs broke, hundreds of "rag-doll" lambs dead in a field because researchers intentionally left them out in the cold—paint a picture of the USDA's callous indifference to animal suffering.
Other than a few tepid statements, the USDA has done little over the past week to refute the notion that apathy toward animal suffering is endemic at the agency. The agency's anemic response certainly raises questions about what other horrors might yet be discovered at the other federal Agricultural Research Services facilities in about a dozen states across the country that conduct research aimed at making animal production more profitable.
This week the ASPCA told the USDA that our taxpayer-funded agencies must take their marching orders from the public and not industry alone (see our full letter below). Americans will not tolerate needless animal suffering and won't allow our public institutions to endorse and perpetrate cruelty.
We urge the USDA to directly address the allegations of abuse at the USMARC and make the structural and cultural changes necessary to ensure that this inexcusable brutality never happens again. We will not turn the page on the gut-wrenching images of abuse until the USDA accepts responsibility and decides to be a leader in eradicating cruelty.
Paddy is a shy cat who loves attention from his favorite humans. He can be a little nervous when he first meets new people, but don't be fooled—this affectionate guy would be thrilled to curl up by your side for plenty of cat naps! With a little space to himself and some yummy treats, he'll come out of his shell for plenty of snuggles in no time.
This handsome cat has a few special medical conditions and can be particular about his litter box, but our Behavioral team can walk you through the best ways to manage his needs. Adopt Paddy today!
Paddy is available for adoption at the ASPCA Adoption Center. If you are interested in adopting, please call our Adoptions Department in New York City at (212) 876-7700 ext. 4120. To learn more about Paddy, please visit his profile page.
To learn more about Paddy and to watch him in action, check out the video below!
The National Chicken Council calculates that about 1.25 billion chicken wings will be consumed this Sunday, February 1, when much of America will be watching the biggest football game of the year.
When you see a platter piled high with wings, remember that every pair of wings represents an individual chicken. Here's what his life was probably like in today's age of factory farming:
- Could barely fly
The chicken industry has bred chickens to be up to three times bigger than they used to be, but that weight means they often can't walk without pain, never mind get off the ground easily. Slower-growing, healthier chickens can perch and even fly up into low branches of trees.
- Couldn't balance
Some chickens are so incapacitated by their ungainly bodies that they have to use their wings for balance (like crutches) to shuffle to a source of food or water. The practice is sometimes called "wing walking."
- Could barely move
Imagine a football field full of chickens, from one end zone to the other. This is what a typical industrial chicken shed on a factory farm is like: Tens of thousands of birds are packed into giant, windowless structures, living in their own waste. This causes open sores on their chests and feet that can act as gateways to infection. With often less than one square foot of floor space each, birds have no ability to perch, forage or even move easily.
It doesn't have to be this way! The ASPCA's Truth About Chicken campaign is encouraging companies to use more humane practices to finally address the suffering stemming from unnatural growth rates and poor conditions.
In the meantime, if you do plan to purchase wings, look for products bearing trustworthy labels that represent better animal welfare standards, like Certified Humane, Animal Welfare Approved and Global Animal Partnership. Certified farms such as White Oak Pastures, Crystal Lake Farms and Mary's Chicken specialize in breeds with more balanced growth and offer birds much more space to move, enrichment and outdoor access.
If you'd like to see more humanely raised chicken in your local store, please fill out an online supermarket request form at TruthAboutChicken.org.
When an animal survives a harrowing ordeal, it makes it that much more meaningful when they find a loving home. For a tiny Maltese/Yorkie named Chali, a freezing January morning set the stage for a warm, cozy future, and we can't help but think that his "Happy Tail" was written in the cards. Here is his story.
On January 5, 2014, Chali was found wandering as a stray in Crotona Park in the Bronx, New York. It was the height of the "Polar Vortex," and temperatures that day hovered in the low 20s. A Good Samaritan spotted Chali lost in the snow and brought him to the ASPCA. At only seven pounds, the four-year-old pup was shy, shivering, and in desperate need of a home.
At the ASPCA Animal Hospital, Chali received a medical exam and was deemed healthy. He was soon neutered and placed into our office foster program so he could recover from his surgery in the care of our staff until he was ready for adoption.
While all of this was happening, an ASPCA employee named Missy G. was working on plans for the ASPCA Bergh Ball, an annual fundraising event in New York City. A member of our Special Events Department, Missy was coordinating a photo shoot for a custom deck of playing cards featuring adoptable animals from the ASPCA. By chance, the day of the photo shoot was the same day Chali came to the Adoption Center.
"I picked him up and brought him to the shoot," Missy recalls. "He was the first dog we shot and he ended up being the Ace of Clubs." While Missy worked on the project over the next few weeks, she continued to visit Chali, and slowly but surely, he stole her heart. "On the last day of shooting, I decided I couldn't just leave him behind and I brought him home with me," she says.
Missy changed Chali's name to Rocky, and in the year since his adoption, the pair has become inseparable. He still comes to the ASPCA office for regular visits. "From the moment he walked into our home, it was like he had always been there," Missy beams. "He was the perfect addition to our family and I love him more than anything."
It's hard to believe that anyone could abandon a dog like Rocky, but it's clear that he is finally where he was always meant to be. He may have been the "Ace of Clubs" in our deck of cards, but to Missy, he's the King of Hearts.


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17 Comments
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Where Akuto's troubles get even worse is when he meets one of the stars of the school, a beautiful young woman named Etou who is the head of the girl's dorm. She gives him words of encouragement and that's all he needs to feel understood enough to think of her as his personal savior. Etou obviously has other plans for him though and starts orchestrating a way for the two of them to meet without Korone at his side. You'd think something like this would be a huge red flag for him considering all that's happened before, but he manages to fall for it pretty easily, though he does get distracted from his plans at times when he starts following Korone and gets to see quite a lot of her panties, as well as her special attribute.
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This Blog is written by Seattle Attorneys Jamie Clausen & Michael Ballnik. It is made available for educational purposes only. Its purpose is to give you general information and a general understanding of the law, not to provide specific legal advice. Reading this blog does not create an attorney client relationship between you and Phinney Estate Law. Because each individual and family is unique, the Blog should not be used as a substitute for legal advice from a licensed professional attorney in your state.
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My Wayfair |
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Torchiere Electric Fireplace is also sometimes listed under the following manufacturer numbers: SEP-BW-4217-FB


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SoundMAGIC ES20 In-Ear Hi-Fi Noise Isolating Stereo Headphones - Gray
"Initial Impressions Out of the box they are not impressing me. At all. Hopefully aggressive burn in with white noise will fix them. Otherwise they are headed for the return heap as defective. I'll update this after 12 hours or so. I won't even bother comparing them with my other 'phones unless the harmonics I mention settle down. Sound Treble: Rolled off. ..." --adevriesc
Soundmagic MP21
"I love these earbuds. At the time of writing, these are literally my favorite in ears ever. While Im sure they cant compete with anything over $200, I've never payed more than $45 for earbuds. At the $20 I payed for these, I could cry at how great they sound. -Bass is slightly boosted, but not overpowering in any way. -Mids are very in control, seem to be very..." --smitty1ky
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Soundmagic E10
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Soundmagic E30
"This is an update to the review after living with several sets of these beauties for 1.5 years....I now have acquired 7 sets of the e30 with varying amount of time on them ranging from brand new to 500 hours and there is so much variation that I don't know which one to review here, but I will continue in part because I am enjoying them so much and would like to help others who are searching for..." --thelostMIDrange
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"Final Audio Design is a relatively new company to the IEM scene, with them releasing their first models in 2009. They are a Japanese company, with their roots extending back to 1974 where they first made high-end MC cartridges and booster transformers. The model that I will be reviewing today is their Heaven IV, which is the second cheapest model in their Heaven IEM series, the most basic one..." --lin0003
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A team of physicists has proposed a way of teleporting energy over long distances. The technique, which is purely theoretical at this point, takes advantage of the strange quantum phenomenon of entanglement where two particles share the same existence. » 1/29/14 1:30pm 1/29/14 1:30pm
The longer you use a computer, the hotter it will get. That seems like just an everyday fact of life, but it might actually be its own law of physics. And, like all phyiscal laws, quantum mechanics apparently violates it. » 6/02/11 9:56am 6/02/11 9:56am
Quantum entanglement says that two particles can become intertwined so that they always share the same properties, even if they're separated in space. Now it seems particles can be entangled in time, too. Who's ready for some serious quantum weirdness? » 1/26/11 5:30pm 1/26/11 5:30pm


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Baseball spring training at City of Palms Park in Fort Myers, Florida, offers sun, the chance to see players in a more relaxed atmosphere and close reach to nearby vacation spots. |
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Hiking, kayaking, disc golfing
Though it's hard to choose, Yosemite is still my favorite. Doubt it will ever lose it's number one ranking.`
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From Baltimore, but have been living in Charlotte lo these last twenty years. Charlotte has changed a lot in that time. I like outdoor activities and making new friends with common interests.
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Dr. Frank Howard (deceased)
Year Inducted: 1987
Born: Died: September 29,1988 San Rafael, CA In 1929, Howard bought a pair of skis back with him from trip to He was the first ski movie producer in the West. He joined John Jay and Becker Films to make the official movie of the 1960 Squaw Valley Olympics. He arranged for Warren Miller's first public show in


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Martha Stewart: Pinterest Has a Copyright Issue
Oct. 16 (Bloomberg) -- Martha Stewart talks to Bloomberg Television's Stephanie Ruhle about social media and her opinion of Pinterest. (Source: Bloomberg)
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RO Williams
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RE: sam hutchins still 47429369
I added the photo I had on file.
Added by
on Feb 12, 2015 5:13 PM
Leon Renfro
Thank you so much for the family photo.
Added by
on Feb 05, 2015 10:14 AM
carol phillips mciver
TJ Smith Jr
beautiful job on this memorial. thanks for the pics and newspaper article. did they ever find the murderer?
Added by
carol phillips mciver
on Jan 22, 2015 10:34 PM
Fran Bundy
RE: Robert Lynn Brudon
Yes, it's happened to me many times as well, so I knew what happened. Thank you, Richard.
Added by
Fran Bundy
on Jan 19, 2015 4:38 AM
Fran Bundy
Robert Lynn Brudon
Thanks for the info & pictures, too.
I believe two pictures of his marker downloaded.
Could you delete one, please?
Thanks again, Richard. I sincerely enjoy working with you...your work is thorough.
Added by
Fran Bundy
on Jan 18, 2015 7:29 AM
Eugene Corbett
Thank you. Do you have any further information on these two? Do you know where they are buried?
Added by
on Jan 15, 2015 8:38 PM
Susan Williams
RE: Henry Jumper Sr. 48264718
Thanks Mr. Williams. But i did a survey of the Springfield Cemetery and the ODOM cemetery in 1999. Obviously these stones were moved from the Odom Cemetery and they were NOT in Springfield Cemetery in 1999. Thanks again!
Added by
Susan Williams
on Jan 10, 2015 12:13 PM
carol phillips mciver
RE: Keziah Antoinette Phillips
sorry to keep bothering you but.... I have been wanting to have some of the broken gravestones repaired and many others cleaned. Folk Mortuary in Williston not interested. Would you know anyone local??
Added by
carol phillips mciver
on Jan 08, 2015 4:24 PM
Susan Williams
RE: Henry Jumper Sr. 48264718
Do you know when these stones were moved? Or is there still a stone in the Odom cemetery too? They were in the Odom cemetery when I went there in 1999 and wrote all the names down. Also did Springfield survey around same time. They are not on my Springfield list which means they were moved after 1999.
Added by
Susan Williams
on Jan 07, 2015 3:58 PM
carol phillips mciver
Keziah Antoinette Phillips
at Rocky Swamp Methodist Church near Neeses, S.C. Do you get over there much? It appears that her gravestone says her year of death was 1871 but I have legal documents showing her alive until 1774 and a probate court document dated Sept 1874 that says that she died in Feb. 1874. Would love to have you double check the grave stone date of death....
If it conflicts it won't be the first time! ugh!
Added by
carol phillips mciver
on Jan 06, 2015 9:16 PM
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Firestein, Gary S. MD
From the Department of Medicine and the Division of Rheumatology, Allergy, and Immunology, University of California, San Diego School of Medicine, La Jolla, California.
Reprints: Gary S. Firestein, Professor of Medicine, Chief of Rheumatology, Allergy, and Immunology, University of California, San Diego School of Medicine, 9500 Gilman Drive BSB, Room 5098, Mail Code 0656, La Jolla, CA 92093. E-mail: firstname.lastname@example.com.
Although much is known about the etiology and pathogenesis of rheumatoid arthritis (RA), our understanding of the immune pathways remains incomplete. The observed clinical and pathologic manifestations result from activation of several interrelated immune pathways. Current concepts of RA pathogenesis, supported by animal models, laboratory studies, and clinical observation, have reestablished and revised some of the original views. Early proposals emphasized the importance of autoantibodies and immune complexes in the initiation of RA, suggested a role for T cells in the inflammatory response characteristic of RA, and based disease perpetuation on an imbalance in the cytokine networks. We now recognize that each of these interrelated mechanisms significantly contributes to RA pathogenesis, including T cells that can help initiate and perpetuate the disease. This article reviews the major components and immune pathways involved in RA and briefly discusses the animal models that contribute to our understanding. Although a unified theory of RA pathogenesis may not be possible at this time, a paradigm is presented that considers the immune pathways that contribute to disease progression and joint destruction. These pathways may have important implications for treatment, because their modulation by biologic response modifiers (BRMs) directed toward specific targets provides benefits to patients with RA. BRMs are a new class of therapeutic agents derived from biologically active molecules and designed to modulate specific immune or inflammatory pathways. Although currently approved BRMs still have limitations, choosing an appropriate target, possibly early rather than late in the immune response, might result in new and improved therapies for RA.
Rheumatoid arthritis (RA) is a complex inflammatory disease of synovial joints, especially the small joints of the hands and feet, that is characterized by joint destruction and chronic disability. With a population point prevalence of 1%,1 RA is responsible for a significant socioeconomic burden.2 This burden results not only from direct medical costs associated with substantial health resource utilization, but also from high indirect and intangible costs related to lost productivity and decreased quality of life. Recent estimates suggest that indirect costs may account for as much as two thirds of the almost $16 billion annual cost of RA.2
Although rheumatic diseases were recognized at the time of Hippocrates, what has come to be known as RA was first recognized in the 17th century and named by Garrod in 1859. It was definitively described as a clinical entity by Charles Short in 1957. Its complexity was immediately recognized, but despite much immunologic research and the identification of multiple cells and pathways that contribute to its pathogenesis, the underlying etiology and pathogenesis are still not completely understood.
This review discusses our present knowledge of the pathogenic mechanisms of RA. Although we have revisited some of the early views regarding the mechanisms that support inflammation and joint destruction, significant progress has been made in our understanding of the disease. This understanding can be of benefit in developing appropriate therapy through modulation of immune pathways.
Views of RA have undergone several incarnations as new mechanisms and pathways have been uncovered and added to the growing immunologic literature regarding its pathogenesis. RA was initially considered an autoimmune disease based in large part on the identification of rheumatoid factor (RF) in the sera of patients with RA and the characterization of these factors as autoantibodies.3 Zvaifler4 and others subsequently proposed that RA represents a localized immune complex disease characterized by production of RF in the synovium, the formation of RF-immune complexes that fix complement with the ensuing consumption of complement within the joint, and the recruitment of a variety of cells (eg, T cells, B cells, macrophages) that become activated and contribute to inflammation and joint damage. The immune-complex hypothesis was reasonable, especially because the presence of RF was determined to be predictive of more aggressive disease. However, it did not account for the absence of RF in some patients with RA, the presence of RF in patients with other diseases, the presence of RF in a proportion of normal individuals, and other features of the disease.
The search for additional mechanisms implicated a role for T cells in RA pathogenesis and resulted in the identification of immunogenetic components. Using allogeneic mixed lymphocyte reactions, Stastny et al5 demonstrated a relationship between RA and specific human leukocyte antigen (HLA)-DR genes of the major histocompatability complex (MHC). This was the first evidence of a genetic component, and it was a notable finding because HLA is a key molecule responsible for the presentation of antigen to T cells by antigen-presenting cells (APCs) such as macrophages and dendritic cells. Antigen presentation is also one of the signals required for T-cell costimulation and activation, early events in the adaptive immune response.
It subsequently became clear that not only is HLA integral to the immune response, but that the RA associate maps to a specific gene locus coding for the third hypervariable region of the DRβ chain.6 This epitope may predict susceptibility and disease severity.7 One possible mechanism is that this molecule binds an arthritogenic peptide resulting in T-cell activation and inflammation in susceptible individuals. However, caveats associated with this mechanism included the lack of identification of a specific reactive peptide, the existence of heterogeneous allele associations, and the multiple functions of HLA in the immune response. Nevertheless, the implication of T cells in the orchestration of RA pathogenesis was a major breakthrough and is supported by the fact that many of the animal models of arthritis are T cell-dependent (eg, collagen- and adjuvant-induced arthritis).
By the mid-1980s, cytokines produced in a variety of immune and inflammatory cells had been identified, and these molecules were considered prominent in the RA disease process. A chaotic cytokine network was simplified by the characterization of a regulatory network that took into account the major cell types in the synovium, their products, and their actions. For instance, the production of the T cell–associated cytokines interferon-γ (IFN-γ) and interleukin-2 (IL-2) within the synovium is relatively low in RA.8 The fibroblast- and macrophage-like synoviocytes in the intimal lining of the synovium produce factors that activate adjacent cells to maintain the inflammatory response, with T cells as well as B cells and macrophages accumulating in the sublining layer.9 The predominance of these macrophage- and fibroblast-derived cytokines8 pointed to a non-T-cell mechanism for rheumatoid synovitis. The cytokine network was subsequently proposed as a perpetuating mechanism in RA,10 and the imbalance between proinflammatory and antiinflammatory cytokines became the focus of pathogenic mechanisms in RA.
Strong support for the role of the cytokine network in RA was provided by the development and approval of the first biologic response modifiers (BRMs). These BRMs, which specifically target cytokines involved in the inflammatory response, include the anti–tumor necrosis factor (TNF-α) agents etanercept, infliximab, and adalimumab, and the IL-1 inhibitor anakinra. That these BRMs are effective in the management of RA and have been beneficial in a proportion of patients, providing not only symptomatic relief, but also slowing radiographic progression, confirms the importance of cytokines. However, these agents are dramatically effective in only approximately 40% of patients, and even in these patients, the requirement for continuous therapy suggests that additional stimuli are required to orchestrate the regulation of cytokine production.
Renewed interest in autoantibodies as precipitating factors in RA pathogenesis resulted in part from the serendipitous development of a spontaneous mouse model of arthritis that is mediated by immune complex formation. The K/BxN mouse is a transgenic mouse characterized by a chronic erosive polyarthritis that shows similarities to human inflammatory RA, including pannus formation, synoviocyte proliferation, and synovitis.11 Propagation of this arthritis is dependent on B-cell secretion of arthritogenic autoantibodies.12 These autoantibodies bind to the self-antigen glucose-6-phosphate isomerase (GPI), a ubiquitously expressed cytosolic enzyme involved in glycolysis.13 The disease in these mice initially starts as a T cell-dependent response to GPI in which autoreactive T cells recruit anti-GPI B cells, which then differentiate into plasma cells producing arthritogenic autoantibodies (anti-GPI-IgG). The subsequent initiation of synovitis is solely dependent on these autoantibodies, because transfer of sera or purified anti-GPI antibody from K/BxN mice into naive mice results in the transient development of arthritic joints.11,12,14 Repeated administration of K/BxN serum or antibody is required to maintain the disease. The proposed mechanism for these effects is induction of the inflammatory cascade resulting from the formation of GPI–anti-GPI immune complexes on articular surfaces.15 The inflammatory cascade appears to be primarily mediated by the alternative complement pathway,15 but the K/BxN model is also clearly dependent on the cytokine network. In vivo studies in cytokine knockout mice suggest an absolute requirement for IL-1 and a lesser role for TNF in disease development.16 This model not only demonstrates the importance of autoantibodies as a catalyst for the inflammatory response, but also highlights the role of T cells and shows that there is a clear relationship among the various proposed pathogenic mechanisms.
Although the presence of these autoantibodies suggests a role of B cells in RA (Fig. 1), a joint-specific self-antigen may not be a prerequisite for induction of RA. In the case of GPI, its actual role in human RA is unclear, because there is a low prevalence and an absence of specificity of GPI antibodies in RA.17 Hence, GPI–anti-GPI immune complexes are not likely to be a major driving force in disease pathogenesis. There are many other putative antigens implicated in RA, including heat shock proteins, collagen, heavy chain binding protein, and cyclic citrullinated peptides (CCPs).18 These molecules could contribute to the pathogenesis of RA, because the resulting immune complex formation can potentially promote complement fixation and activation of immune cells (Fig. 1). However, autoantibodies are not likely to be the sole etiologic agents, because autoreactivity often precedes clinical RA by many years.19 In particular, anti-CCP antibodies might be predictive of RA, with presence in sera predating onset of symptoms.20 Anti-CCP antibodies also have >90% specificity for RA21 with a high predictive value for development of clinical disease, disease severity, and radiographic damage.19,20,22–24
Just as autoantibodies and immune complexes are being reestablished in the hierarchy of immunoinflammatory events in RA, T cells have also been implicated as primary mediators in the orchestration of RA. This role for T cells represents one of the latest developments in our understanding of RA and is important not only from the mechanistic standpoint, but also from the clinical perspective.25
In a manner similar to that of autoantibodies discussed here, the concept of a central role for T cells was supported by another spontaneous mouse model. The SKG mouse is a T cell-dependent model of inflammatory arthritis that has clinical and histologic similarities with human RA.25,26 In the SKG mouse, a mutation in the ZAP-70 signal transduction gene involved in T-cell activation results in abnormal thymic selection of autoreactive T cells. Instead of being deleted to prevent autoimmunity, there is positive selection of these autoreactive T cells, which survive and become arthritogenic.
Although the SKG model suggests that T cells can spontaneously cause inflammatory arthritis in RA, to understand how this occurs, it is important to understand that activation of naive T cells requires 2 distinct but contemporaneous ligation events (Fig. 2). 27 The first event consists of presentation by an APC of an MHC–antigen complex with reciprocal binding to the T-cell receptor. The second signal occurring in temporal proximity is ligation of a costimulation molecule on the APC with its cognate receptor molecule on the T cell. Binding of the MHC–antigen complex to the T cell without costimulation results in hyporesponsive T cells (ie, anergy).28 In contrast, binding of both costimulatory signals results in T-cell activation with the consequences of T-cell antigen responsiveness. Several costimulatory pairs have been described, some of which activate T cells and some of which attenuate the T-cell response. Of the pairs that activate T cells, CD28 and CD80/CD86 are among the best characterized.27 This pathway is the target for abatacept, a new BRM that interferes with costimulation. Although this approach and its clinical implications are discussed elsewhere in this supplement,29 the clinical efficacy observed using costimulation modulation supports a role of T cells in many patients with RA.
T cells may contribute to the inflammatory response because they not only have specific effector functions, but they also activate or interact with other cells that perpetuate inflammation and joint destruction (Fig. 3). These interactions include those with B cells, which may then be induced to produce autoantibodies; macrophages, fibroblast-like synoviocytes, and chondrocytes, all of which can release proteases and other effector molecules; and osteoclasts.9 These latter cells are of particular importance because they are responsible for bone resorption and their activation accelerates joint destruction in patients with RA.30
There is also intersection between T cells and the cytokine pathway through T cell-derived cytokines and cytokines released by other T cell-activated immune cells. Two T cell-derived cytokines of potential importance in RA are IFN-γ and IL-17. Although only small amounts of IFN-γ are produced by synovial T cells,8,31 the presence of this cytokine could be important. First, IFN-γ serves as a marker for the subset of activated T cells known as TH1 helper cells. These cells promote and amplify autoimmune diseases, and it may be a shift in the ratio of TH1 and TH2 cells that helps perpetuate pathogenic mechanisms.32,33 IFN-γ also has a direct effect on inflammation by increasing MHC class II expression as well as priming macrophages to produce inflammatory and tissue-damaging mediators such as TNF-α, proteases, reactive oxygen species, and nitric oxide.34
Another notable T cell-derived cytokine detected in RA synovium is IL-17. This cytokine, which shares many functions with IL-1 and TNF-α, is produced in rheumatoid synovium by T cells.35,36 The consequences of IL-17 action have led to the suggestion that it might serve as a "missing link" between T-cell accumulation/activation and the downstream mechanisms leading to inflammation and joint destruction.35 IL-17 can amplify the production of proinflammatory cytokines by fibroblasts and macrophages and can also promote cell adhesion molecules, thereby enhancing infiltration of inflammatory cells into the joint. It also induces production of matrix metalloproteinases (MMPs) and shifts the balance of bone metabolism toward osteoclastogenesis with subsequent bone resorption.35
Although IL-17 by itself can induce MMP production and cause cartilage destruction, suboptimal concentrations are synergistic when combined with the proinflammatory cytokines TNF-α and IL-1.37 Based on this range of activities, IL-17 has been considered a potential target for therapy. In fact, treatment of a mouse model of arthritis with a neutralizing antibody against IL-17 results in reduced inflammation and joint damage.38
If T cells produce cytokines and perform other effector functions in the joint, the inciting antigen is clearly relevant. Although many identified antigens have been considered such as RF, GPI, CCP, and others as previously mentioned, no single antigen fits all the requirements for explaining the disease.9 Indeed, initiating antigens might be distinct from perpetuating epitopes. Either antigen spread or antigen replacement might be a driving force in established disease. Furthermore, as also previously suggested with regard to GPI, the inciting stimulus need not be a joint-associated antigen. Although some of the currently identified autoantibodies are joint-specific such as type-2 collagen and proteoglycans, RF and CCP are systemic antigens that have been implicated.9
In addition to the previously mentioned immune cells, recent work has identified a subpopulation of activated synovial fibroblasts that are present in RA and have characteristics that clearly distinguish them from other synovial fibroblasts.39,40 These fibroblasts within the RA synovium are more aggressive than normal or osteoarthritis synoviocytes. Their activation induces an increase in adhesion molecules, which enhances their attachment to articular cartilage and increases their invasiveness into the extracellular matrix. When activated, they also release MMPs and other proteolytic enzymes, which contribute to joint degradation by digesting matrix proteins such as collagen and proteoglycans. Additionally, the RA synovial fibroblasts appear to enhance T- and B-cell survival in the synovium by preventing apoptosis, potentially prolonging the immune effector functions of these cells.
Evidence suggests that in RA, this subpopulation of synovial fibroblasts might become permanently imprinted to express the more aggressive phenotype. When coimplanted with normal human cartilage in severe combined immunodeficient mice, they retain their aggressive behavior even in the absence of other inflammatory cells.41 The factors initiating activation and imprinting have not been fully characterized, although cytokine-dependent and -independent mechanisms have been described.40
After many years of experimental and clinical investigation into the pathogenesis of RA, we have a better, albeit still incomplete, understanding of the disease process. Interestingly, we have come full circle in our concepts, with the roles of immune complexes and T cells that were initially postulated to be central to RA pathogenesis again coming into focus as primary mediators in the initiation and perpetuation of the disease.
Although RA is a complex disease with multiple interacting mechanisms that contribute to inflammation and joint destruction, a possible paradigm that takes into account the major features can be described as shown in Figure 4. In this model, both predetermined and random events contribute to the initiation of the disease. The predetermined aspect is the genetic component, which suggests that certain individuals carry a genotype for autoreactivity that may precede disease onset. The random aspect is represented by environmental influences that might activate innate immunity. This primordial defense system is an evolutionary adaptation that enables rapid recognition and elimination of pathogens and is considered the first line of an organism's immune defense.
Processing an unspecified but not necessarily rheumatoid-specific antigen by dendritic cells and presentation to T cells in conjunction with the costimulatory signal activates the T cells that then help orchestrate many of the downstream pathways. This processing and presentation of antigen likely occurs in central lymphoid organs and initiates the adaptive immune response, an organism's second line of defense that results in expansion of cell populations recognizing specific antigens. The initiation of adaptive immunity produces a clonal expansion of T cells with subsequent migration to the synovium where cytokines are produced and where the T cells interact with synoviocytes, macrophages, and B cells to promote inflammation. Under appropriate conditions, loss of tolerance related to either genetic predisposition or the T-cell repertoire can result in an autoimmune response to particular antigens newly exposed during inflammatory degradation of the joint.
With the identification of multiple cell types and various cytokines providing opportunities for new interventions, these concepts have therapeutic implications and have shaped our current approach to RA management. Furthermore, the complexity and redundancy of the regulatory mechanisms combined with the observed interpatient variability in the disease process explains why some patients may respond to a particular therapy whereas others do not, especially when targeting pathways downstream of key regulators of immunologic events.
The ability to construct biologically active molecules has resulted in the introduction of BRMs as therapeutic agents. By modulating immune and cellular responses, BRMs have expanded our resources for therapy as well as for further investigation of the disease process. Although currently approved BRMs represent a major step forward in the treatment of RA, demonstrating both symptomatic efficacy and disease modification, they are not without limitations. Choosing an appropriate therapeutic target is crucial to bringing greater benefits to more patients. It is possible that modulation of selected events early rather than late in the immune response can have the effect of modulating pathways that are of particular importance in the pathogenic process. Agents currently in clinical trials such as abatacept (discussed in this supplement by Kremer29), as well as many still in development (reviewed in this supplement by Genovese42), have generated optimism that we may eventually control the progressive course of RA, reducing both the economic and patient burden.
This article has been cited 55 time(s).
rheumatoid arthritis; pathogenesis; autoimmunity; immune complexes; T cells; B cells; cytokines
© 2005 Lippincott Williams & Wilkins, Inc.
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in alchemy, substance thought to be capable of changing base metals into gold. The same term, more fully elixir vitae, "elixir of life," was given to the substance that would indefinitely prolong life-a liquid that was believed to be allied with the philosopher's stone. Chinese Taoists not only sought the "pill of immortality" but developed techniques (meditation, breathing exercises, diet) that were thought to confer immortality by internal alchemy.


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Organised yearly by SATCAR, this festival rewards the best car advertising films, since 1989. It offers experts from the world of advertising the opportunity to promote themselves by showing their best and most original creative works. Carmakers' films and automobile world films are eligible to enter the competition.
An international jury, made up of celebrities and professionals from the world of automobile, advertising, media and the cinema, will award the Marcus (the festival's trophy) during a gala evening, opened to the public.
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Story Created: Jul 11, 2014 at 7:31 AM CDT
Story Updated: Jul 11, 2014 at 7:31 AM CDT
AKRON, Iowa (AP) - A man sought as a witness to the suspicious deaths of two elderly people in northwest Iowa has been found in Wisconsin.
Authorities say 44-year-old Jonathan Neunaber was detained by police in La Crosse, Wisconsin, after he was stopped for a traffic violation on Thursday night. He was held on the Iowa warrant for a material witness.
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- 1 bedrooms
- 1 bathrooms
- Sleeps 4
- Apartment
Description from the owner
You and your pets friends are welcome to our "100% smoke-free" studio apartment!
It is cozy and bright, has a wide living room/kitchen with a sofa-bed, a comfortable bedroom, a bathroom with shower and a beautiful wide terrace with table and chairs. Four people will fit comfortably.
The apartment is on the first floor of two.
If you have problems climbing stairs or have small kids don't worry, there is a lift from the apartment floor to the garages area.
You'll have a covered garage available, only note that access to the garages is allowed only to vehicles with a maximum height 2.00 meters and is not intended to vehicles with lowered suspension.
Available ...Read more
Appartamento Vacanze Il Riccio
Veneto - Venice, Italy
What's Nearby:
Additional Location Information
The apartment is located in a residential neighborhood that offers, within a few hundred meters, bars, bakeries and pizzerias, grocery stores, clothing and various, banks, post office, etc.
Within few kilometers you reach Padua or the spa area (Abano Terme, Montegrotto Terme, etc) and "Colli Euganei".
It's easy to go downtown Padova using the public transportation.
The bus stop is 700 mt away, then take the streetcar to get downtown or to reach the train station or coach station to go to other destinations.
It's always advisable to check in advance routes, timetables and connections.
Surely having a car available it is better so that you can visit all the fascinating spots around that are not reachable by public transportation.
More About This Location
City vacations, Rural retreats
Getting There
Car is recommended
Last updated on December 10, 2014
Not available for your dates? Check availability for 1,133 other Veneto - Venice rentals
Check Availability for Veneto - Venice
- A/C or climate control
- Soap/Shampoo Provided
- Linens Provided
- Washing Machine
- Towels Provided
- Local Guides/Maps
Phone / Internet
- Internet Access
Property Features
- Parking
- Freezer
- Refrigerator
- Stove or Oven
- Television
- Books
- Stereo or CD player
- Outdoor Dining Area
- Balcony or terrace
- Garage
- Pet friendly - yes
- Smoking allowed - no
- Suitable for children - yes
- Suitable for the elderly - yes
- Wheelchair accessible - no
Have you stayed here?
This rental is awaiting reviews from past guests. Help out travelers and the owner by being the first to write a review!
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I brew big beers, usually 18 to 23 pounds grain and 8 to 10% ABV using dry yeast only. Have been reading about aerating big beer wort to give the yeast enough oxygen but does this apply to dry yeast? From the Danstar FAQ: Quote: I always aerate my wort when using liquid yeast. Do I need to aerate the wort before pitching dry yeast? No, there is no need to aerate the wort but it does not harm the yeast either. During its aerobic production, dry yeast accumulates sufficient amounts of unsaturated fatty acids and sterols to produce enough biomass in the first stage of fermentation. The only reason to aerate the wort when using wet yeast is to provide the yeast with oxygen so that it can produce sterols and unsaturated fatty acids which are important parts of the cell membrane and therefore essential for biomass production. If the slurry from dry yeast fermentation is re-pitched from one batch of beer to another, the wort has to be aerated as with any liquid yeast. Does the above apply to big beers or is it better to aerate? I typically hold drain tube from cooled wort in brew pot well above the wort level in the fermenting bucket. Is further aerating necessary for big beers? If so, how to aerate? An aquarium pump for a 5 gal tank and a small stone cost $10. Devises that use oxygen cylinders are faster and provide more oxygen but they cost $40 and more. If you aerate what do you use. Can a small fuel filter be used to trap impurities from the air?
"Ask not what your country can brew for you ; ask what you can brew for your country." "ich braute dieses Bier mit meinem Hund" (Life is indeed short: Get a Beagle and a Beer
I have heard on brewstrong that using an o2 tank with a difuser stone works amazingly well. I have yet to try this yet though.
Wyeast has an article on their site about oxygenation: http://www.wyeastlab.com/hb_oxygenation.cfm Even though it might not be strictly *necessary* with dry yeast, it's a good habit to get into. From my reading of the article, it might be a good idea to let a little kettle trub get into the fermenter if you're not using pure O2. Another interesting idea that New Belgium has tried is using olive oil in place of aeration:http://www.homebrewtalk.com/f13/usin...-oxygen-47872/http://www.brewcrazy.com/hull-olive-oil-thesis.pdf Edited to add: As far as how I do it, I got the kit from William's Brewing which puts the stone on the end of a metal tube. I figured that way, I could be sure the O2 bubbles would have maximum contact time with the wort before reaching the top. I'm thinking about getting another stone, though (just the stone) for aerating starters. I didn't think that was too necessary with a stir plate, but I'm not sure.
I typically hold drain tube from cooled wort in brew pot well above the wort level in the fermenting bucket. --> You're probably getting plenty of aeration at that point --> If you want more aeration, put a screened funnel into the carboy and empty your drain tube through it --> If you want to take it further, get a Siphon Spray Wort Aerator for $4 from your fave LHBS (this is what I use) I use an aquarium pump with an inline filter for my yeast starters. Hard to tell if you're considering aerating your wort after pitching the yeast. I'd avoid this because at some point you are just oxidizing your brew. I always make a starter and aerate the wort prior to pitching, regardless of whether or not I use dry or liquid yeast. I think it's a better practice.
Ex fermentum, scientia.
From the research I have done and have been using. .5 micron stone for pure oxygen. Smaller bubbles dissolve easier in your wort. You do not want the oxygen bubble to reach the top of your wort. You want them to dissipate within the wort before they reach the top. I do 1 ppm for 1 minute per the Yeast book recommendation by Chris White. Not sure what the optimal setting would be for a 2 micron stone. Oxygen Welding Tank - http://www.harborfreight.com/20-cubi...der-92810.html Get an empty from Harbor Freight with 20% off coupon and exchange it at a gas supply place for a full one. Supposedly medical tanks and welding tanks are filled exactly the same way from the same source, one is just is "certified". Bigger upfront investment but you wont have to constantly mess with getting the small ones at the home improvement stores, The 20 cubic tank will last you a long, long time. Add this - http://www.amazon.com/Oxygen-Regulat...ygen+meter+1-4 Whatever you get needs a CGA450 connection for the tank. It is great to be able to precisely control the flow of oxygen. and a stainless steel oxygen wand and you are set. The wand allows you to quickly / easily position the stone at the bottom of your fermenter. I did a fair amount of research before I decided on this route and so far I have had excellent results. If you decide to go aquarium pump route - get the 2 micron stone and a inline Hepa filter. Most of the big online retailers carry them.
Yeast need oxygen. Especially with high OG wort, atmospheric aeration in inadequate. Buy an oxygenation stone, pitch adequate yeast, your beer will dramatically improve. One of the best beer making investments.
I use a graut mixer attached to my drill for aerating my worts and that works fine for me...
Disposable oxygen canisters from Lowes or HD go for around $7. I use a regulator from Williams (best price I've found) and a SS stone from my LHBS. No HEPA filter and no problem with infection provided you sanitize everything and boil the stone to clean it. I get around 6 batches per tank. There was a big improvement in my finished product.


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Bhekuli Biya en
Bhekuli Biya (Frog Marriage) is a mimic act played by young village girls in Assam. When there is no rain for days together during the months of cultivation, they capture two frogs and get them "married", going through all the customs of a usual Assamese marriage. Usually two frogs are caught in order to make the pair. Sometimes there is only one frog, the "bridegroom", for whom a special cloth doll is made to be the "bride". They are bathed, the usual marriage-songs are sung, the conch-shells sounded and the "guests" entertained. At the end of the ceremony, the bride and the groom are placed on a tiny rafter and allowed to float on a river. Frogs and toads are always associated with rains. Orinoco Indians hold toads to be gods of rains and never kill them; some Europeans also think that killing a frog will bring rains. Some women in Tamil Nadu capture a frog and pour water over it when the rains start in order to bring more rain-water. The association of toads with rains is a superstition. But application of water during the rites implies a trace of magic. Bathing the frogs is a symbolic act in order to induce rains. In certain parts of Russia, there was a custom in which a [ - ]


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South Beach Swimsuits was founded in 2004. We are a family owned and operated company. South Beach Swimsuits carries everything from sizzling swimsuits, elegant cruisewear to hot and sexy spring break bikinis. We strive to make your swimsuit purchase as pleasant and hassle free as possible. Our highly trained swimwear associates will be happy to speak with you over the phone regarding sizing, color and styles that flatter your figure.
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Customer service and satisfaction are our number one priorities.
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First, Christians were banned in Dearbornistan. Now, it's Jews who are illegal. Why not just declare the place an outpost of Saudi Arabia and be done with the whole business.
"On 9-14-2012, Dearborn Fordson High School principal called the police on me for driving with 2 Israeli flags on my truck.
When the students began their assault he rolled down his window asking them to stop. After they pulled him over the police used the rolled down window as a pretext to accuse him of instigating the altercation. While being questioned by the police in front of the high school the reader received death threats. The police denied hearing them though the individuals involved were only a few feet away.
"The Dearborn police were one car behind me when this student threw a bottle on my windshield. The police did not stop the student, but instead stopped me for 30 minutes asking me why I would display Israeli flags on my truck."
This is how hellholes like Malmo get started. When the law becomes a tool for enforcing Muslim prejudices, then equal rights go out the window and police lecture anyone attacked by Muslims on what they did to provoke the attack.
But it's not just Dearborn. The consensus of our governing elites is that making a movie mocking Mohammed is a crime that deserves to be punished. So why not driving with an Israeli flag as well? Where do we draw the line? Anywhere Muslim violence tells us to.
Daniel Greenfield is a blogger, columnist and freelance photographer born in Israel, who maintains his own blog, Sultan Knish.
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Judy and Bernie have a wonderful old home in historic Milan, and have restored it beautifully. We stayed in the Hope room, which I recommend as it is on the end of one side of the house and very private, with a private bath across the hall. The bath is enormous, with everything you could think to want readily available.... More
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- Angel Welcome Bed And Breakfast Milan, Ohio


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Almeida had a goal and an assist in Friday's 4-2 loss to No. 3 Denver before a home sellout crowd of 7,884 at Conte Forum. He then added two more assists in a 5-1 victory at New Hampshire Saturday
The senior forward now has registered two goals and three assists in five games.
The sellout on Friday was BC's fourth straight in regular season play for the Eagles.The loss to Denver was the first home-opener defeat for the Eagles since 2005-06, 2-1 to Maine.
BC (3-1) is ranked No. 1 in the USA Today/USA Hockey Magazine weekly national poll ,and No. 2 in the USCHO poll.
BC is home Friday night to the University of Massachusetts (1-1-1)


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Sunderland Football Club
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Bruce linked with Cattermole
15 Jun 2009 - 14:56:37
New Sunderland manager Steve Bruce plans to snap up Lee Cattermole from the club he has just left - Wigan Athletic.
Bruce signed Cattermole from Middlesbrough last summer and the England Under-21 international midfielder enjoyed an impressive season with the Latics.
However, the combative midfielder is not thinking about a possible transfer until after the European Under 21 Championship.
"I had a good year last year and he (Steve Bruce) brought me to Wigan," Cattermole told the Sunderland Echo.
"It's a bit of a shame, but that's football. Managers change, players change all the time so hopefully I'll be able to do the same for Roberto Martinez.
"I obviously really enjoyed last year and there's a lot of changes at Wigan - we've lost our manager and our staff now.
"But I'm going to concentrate on this tournament and get back and see what the situation is with Wigan and meet the new manager and see how it goes."
Related Sunderland News
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Research study participants play a crucial role in arthritis research, and much of the research completed at the Arthritis Research Centre of Canada is made possible by the generous contribution of time by people like you. There are many opportunities for you to become involved; however, some patients are hesitant because they believe that all research studies are invasive. The truth is that some studies can be as simple as taking a survey, testing an interactive website or having a knee exam. And remember, your privacy and confidentiality are always protected.
ANSWER-2: A biologic decision aid for patients with rheumatoid arthritis
For more information, visit: |
Individuals Living with INFLAMMATORY ARTHRITIS WE WANT TO HEAR FROM YOU. For many patients living with arthritis, medication taking is a part of everyday life. Dr. Mary De Vera, Assistant Professor at the Faculty of Pharmaceutical Sciences in the University of British Columbia, and the researchers at ARC are conducting focus group sessions to find out patients' experiences with medication taking. We also hope to gain opinions regarding strategies that may help patients improve medication taking. Patients with Rheumatoid Arthritis, Lupus, Polyarthritis, Psoriatic Arthritis, Ankylosing Spondylitis and Gout who are 19 years old or older are being invited to participate in a 2 hour focus group session. Contact: |
Virtual Gout Clinic |
Shoe Orthotics for Knee Osteoarthritis |
Knee Osteoarthritis Walking Program |
Arthritis in the workforce: How do we measure success? |
Staying Active in the Digital Age |
Arthritis Health Journal |
Employment and Arthritis: Making It Work |
E-Health Ethics Researchers from the University of British Columbia and the Arthritis Research Centre of Canada are studying how people with chronic illness use online sources and mobile technologies for health reasons. In 2010, 70% of Canadian Internet users searched for medical or health-related information. For this E-Health project we are currently recruiting males and younger people aged 19 and above with inflammatory arthritis and at least one other chronic condition, as well as health care providers. We want to understand how new technologies affect health care decisions and interactions between patients/consumers and health care providers and identify any emerging ethical issues. For more information: E-Health Ethics Contact: Jenny Leese: |
IPART Study: Susceptibility Factors for Arthritis among Patients with Psoriasis |
Gordon Whitehead
Nadia Prestley


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