text:
There are two things I know about DRM. One is it doesn't work. Two is that people hate it.
Frankly, it's not surprising to me that potential customers of EA's Spore are turning to bittorrent sites to download copies of the game. The pirated copies seem to be more functional than the ones they can buy — the store bought copies may cease to work if they believe you've committed the IP crime of multiple (>3) installs.
But what is remarkable to me is how EA is so scared of piracy that they are in effect suprring the illicit market by voluntarily crippling their own software. They must know this, and yet they make the same choice, time after time, with more and more obnoxious methods. Even Sony is getting the message, so why not EA?
DRM prevents average users from easily making copies, no doubt. It does very little to deter pirates. So in effect, people who would have only bought one copy anyway will at best only buy one copy, and they will increasingly turn to free and unfettered sources, despite the risks.
Imagine, then, if EA took the complete opposite tack and gave the game away for free, with no restrictions other than that you couldn't upload and download content without a paid network account. They could probably open a PayPal account for voluntary donations and do better with the would-be pirates.
If they employed one of the known strategies for putting subscription-based games on physical store shelves, they might even do better overall.


text:
(CNN) -- Authorities in Mississippi are being tight-lipped about the death of a mayoral candidate and the arrest of a man found alone in the candidate's damaged SUV.On Thursday, the Coahoma County Sheriff's Office announced that a suspect, Lawrence Reed, faces a murder charge in the death of Marco McMillian.
Reed, 22, was found in McMillian's wrecked SUV on Tuesday morning and was taken to a hospital. He is in good condition, the Sheriff's Office said Thursday.
On Wednesday, authorities found McMillian's body near a levee between Sherard and Rena Lara, two unincorporated communities about 15 minutes away from Clarksdale in Northwestern Mississippi's Delta region.
Officials have yet to comment on why or how McMillian was killed.
"It's too early in the investigation to know what the motive is," Sheriff's Office spokesman Will Rooker said of McMillian's death.
McMillian's body was taken to the capital, Jackson, for an autopsy.
Patricia McMillian said that even though media reports since her son's death have labeled him as openly gay, his death likely had nothing to do with his sexual orientation.
She told CNN that her son had told only family and friends that he was gay.
"He did not announce in public that he was gay," she said, adding, "I don't think he was attacked because he was gay."
She said that she didn't know Reed.
"We never heard of him," said Amos Unger, Marco McMillian's stepfather.
McMillian's Facebook page shows a glimpse at a man who was politically ambitious. It includes a picture of McMillian posing with President Barack Obama. His campaign motto: "Moving Clarksdale forward."
McMillian's short biography on Facebook said he had spent much of his career raising money for universities after he graduated from Jackson State with a degree in elementary education. He also received a master's in philanthropy and development from Saint Mary's University of Minnesota.
Condolences flooded the page, including one from a man who wrote that McMillian, 34, was one of Clarksdale's best leaders.
"The shocking news of Marco's death is beyond difficult for us to process," his campaign team posted Thursday. "We remember Marco as a bold and passionate public servant, whose faith informed every aspect of his life."
Bill Luckett, who like McMillian was running for mayor as a Democrat, said he thought the politician was "cordial and articulate."
"It's a bizarre situation," Luckett said. "A sad story."
McMillian picked up a host of awards in recent years. In 2009, he received the Thurgood Marshall Prestige Award from the Thurgood Marshall College Fund. In 2004, Ebony magazine recognized him as one of the country's top leaders younger than 30.
His fraternity, Phi Beta Sigma, released a lengthy note about McMillian's accomplishments Thursday.
McMillian "made an incredible difference in his community" it read, adding that he was the executive director of the fraternity from 2007 to 2011.
McMillian secured the first federal contract to raise awareness about HIV and AIDS among African-Americans for the fraternity and helped it form partnerships with organizations such as the U.S. Marine Corps and the Centers for Disease Control and Prevention in discussing the disease.
CNN's Rich Phillips contributed to this report.

subset: commoncrawl


text:
AU Optronics Plunges 6% on Panel Weakness
- Order Reprints
- Print Article
Yesterday, AU Optronics (AUO) closed an eight month high. Today, the stock is down 6%.
What happened? Blame it on panel pricing. SinoPac explains that "[Chimei Innolux and AU Optronics] pulled back sharply after panel prices for monitors dropped 1%- 2%... and TV panel prices stayed flat in late Dec. The market fears that TV panel prices may see further drops in 1Q13."
If AU Optronics only had to worry about the present, then it might not have gotten hit as hard as it has. But Capital Securities Corp. explains says that:
Nov12 revenue of panel makers and component suppliers appeared worse than expected. Dec12 revenue of panel makers and component suppliers is likely to be sluggish. Outlook of the sector appears overshadowed by downside risk in 1Q13. AU Optronics and Chimei Innolux are unlikely to return to profit in 4Q12. Recommend NEUTRAL on AUO and Chimei Innolux.
Take a look at the stock's chart:
Although it's hard to see (I'll get this figured out, I promise), there was clearly a lot of optimism built into the stock, which had rallied more than 75% since Aug. 8.
Clearly, some of that optimism has evaporated today.


text:
Get Em: Cubana Lust Goes In On The Guy In Old Tape For Leaking s3x Tape Online!
Im sure most of ya already heard of a old Cubana Lust sex tape that hit the net. Well here is Cubana Lust addressing that guy in the video who smashed her back in the day and released that old tape on the net. (c) CubanaLust.com
Please click the "Report" button below if the video on this page is not working properly.
Comments will only be displayed by verified emails. No Spamming or Racism.


text:
- Home
- Editor's Desk
- Features
- Columns
- Arts & Culture
- Special Editions
- Advertising
Wednesday July 17, 2019; 11:28 pm EDT
Your Fireworks Guide
Chesapeake Beach
Fireworks go up from a barge anchored off shore at Chesapeake Beach Resort and Spa. View on grounds, from the tiki bar or air-conditioned restaurant (tables reserved), where Split Second Band plays (5-9pm). For water fun with your fireworks, view from Chesapeake Beach Water Park or the beach at neighboring North Beach. For free views, come early to claim your space at Chesapeake Beach or North Beach boardwalk. Or watch by boat: www.chesapeake-beach.md.us.
Herrington Harbour
Fireworks set off from a barge illuminate Herring Bay. Marina grounds are reserved for members. But the view is great from boats, private docks, lawns and beaches. About 9:15pm, Herrington Harbour South, Rose Haven: www.herringtonharbour.com.
Historic St. Mary's City
Pyrotechnics follow Brass and Blues with the Chesapeake Orchestra playing Sousa, Filmore, Clarke, Anderson, Chicago, Blood Sweat and Tears, Prince and James Brown plus Tchaikovsky's 1812 Overture. Music at 7pm: Townhouse Green,
St. Mary's College, St. Mary's City: www.chesapeakeorchestra.org.
Sherwood Forest
See this private community show from the Severn River — your boat or the Harbor Queen, with light snacks and cash bar. 7:30-10:30pm, Annapolis City Dock, $48 w/discounts, rsvp: http://bit.ly/BayWeekly_JulyThirdCruise.
Fireworks rise from a barge anchored in Spa Creek, illuminating Annapolis Harbor, after a United States Naval Academy concert at City Dock (8pm). Town and water views including from the Harbor Queen (7:30-10:30pm, City Dock, $53 w/discounts includes snacks and a cash bar, rsvp: http://bit.ly/BayWeekly_ FireworksCruise): Annapolis, free: www.annapolis.gov.
Fireworks illuminate the Inner Harbor, where the fun starts early when the U.S. Navy Band Cruisers play at the amphitheater (7pm). Come early to find your spot on land or water; for a heightened view, watch from the Top of the World observation floor, World Trade Center ($50 w/discounts), rsvp:
410-837-8439; www.promotionandarts.org.
Bowie Baysox
Fireworks with an extended finale follow the Baysox baseball game with the Trenton Thunder; rsvp for picnic with all-you-can-eat buffet ($31 w/discounts). Picnic 5:30pm, game 6:35pm, Baysox Stadium, Bowie, rsvp: www.baysox.com.
Fireworks shoot from a barge anchored in the Patuxent River, giving the entire island front row seats. A parade of decorated boats show their patriotic colors at noon. rsvp by July 1 to watch aboard the Wm. B. Tennison; bring picnics and beverages.
8pm, Calvert Marine Museum, Solomons, $30: 410-326-2042 x41): 410-326-2042; www.solomonsmaryland.com.
Washington, D.C.
Celebrate America's independence in its capital as the United States Army Presidential Salute Battery blasts cannons in synch with fireworks. Tens of thousands of celebrants gather early on the National Mall for the National Symphony Orchestra's annual concert. The day at 11:45am with the Independence Day parade to the Lincoln Memorial. Prime views throughout the city, including the Capitol, Lincoln Memorial, Jefferson Memorial, FDR Memorial, Iwo Jima Memorial and Ellipse: www.nps.gov.


text:
Services on Demand
Related links
- Cited by Google
- Similars in SciELO
- Similars in Google
Arquivos de Neuro-Psiquiatria
Print version ISSN 0004-282X
Arq. Neuro-Psiquiatr. vol.70 no.1 São Paulo Jan. 2012
Treatment of neuromyelitis optica: an evidence based review
Tratamento da neuromielite óptica: uma revisão baseada em evidências
Douglas SatoI, II; Dagoberto CallegaroII; Marco Aurélio Lana-PeixotoIII; Kazuo FujiharaIV; on behalf of Brazilian Committee for Treatment and Research in Multiple Sclerosis (BCTRIMS)
IDepartment of Neurology, Tohoku University Graduate School of Medicine, Sendai, Japan
IIDepartment of Neurology, Faculty of Medicine, University of São Paulo (USP), São Paulo SP, Brazil
IIICIEM Multiple Sclerosis Research Center, Federal University of Minas Gerais Medical School, Belo Horizonte MG, Brazil
IVDepartment of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine, Sendai, Japan
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterized by severe optic neuritis and transverse myelitis, usually with a relapsing course. Aquaporin-4 antibody is positive in a high percentage of NMO patients and it is directed against this water channel richly expressed on foot processes of astrocytes. Due to the severity of NMO attacks and the high risk for disability, treatment should be instituted as soon as the diagnosis is confirmed. There is increasing evidence that NMO patients respond differently from patients with multiple sclerosis (MS), and, therefore, treatments for MS may not be suitable for NMO. Acute NMO attacks usually are treated with high dose intravenous corticosteroid pulse and plasmapheresis. Maintenance therapy is also required to avoid further attacks and it is based on low-dose oral corticosteroids and non-specific immunosuppressant drugs, like azathioprine and mycophenolate mofetil. New therapy strategies using monoclonal antibodies like rituximab have been tested in NMO, with positive results in open label studies. However, there is no controlled randomized trial to confirm the safety and efficacy for the drugs currently used in NMO.
Key words: neuromyelitis optica, therapy, aquaporin 4, plasmapheresis, steroids, azathioprine, mycophenolic acid, monoclonal antibodies, mitoxantrone, cyclophosphamide, interferon-beta.
Neuromielite óptica (NMO) é uma doença inflamatória do sistema nervoso central caracterizada por grave neurite óptica e mielite transversa, com um curso usualmente recorrente. O anticorpo contra aquaporina-4 é positivo em grande porcentagem dos pacientes com NMO e se liga a este canal de água altamente expresso nos processos pediosos dos astrócitos. Devido à gravidade dos ataques de NMO e ao elevado risco de incapacidade, o tratamento deve ser instituído tão logo o diagnostico seja confirmado. Existem evidências crescentes de que pacientes com NMO respondem de forma diferente dos pacientes com esclerose múltipla (EM) e, portanto, os tratamentos utilizados na EM podem não ser adequados para NMO. Os quadros agudos de NMO são tratados com pulsos de corticosteroides em altas doses e plasmaférese. O tratamento de manutenção também deve ser instituído para evitar ataques subsequentes e é baseado em corticosteroides orais em baixas doses ou imunossupressores, como a azatioprina e o micofenolato mofetil. Novas estratégias de tratamento utilizando anticorpos monoclonais como rituximab têm sido avaliadas para NMO, com resultados positivos em estudos abertos. Entretanto, não existem estudos clínicos controlados, randomizados, para confirmar a segurança e eficácia dos tratamentos atualmente utilizados na NMO.
Palavras-Chave: neuromielite óptica, terapia, aquaporina 4, plasmaferese, esteróides, azatioprina, ácido micofenólico, anticorpos monoclonais, mitoxantrona, ciclofosfamida, interferon-beta.
Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system (CNS) characterized by severe optic neuritis (ON) and transverse myelitis (TM)1. Aquaporin-4 (AQP-4) antibody, also known as NMO-IgG, an autoantibody exclusively detected in the sera of NMO, is directed against AQP-4, a water channel richly expressed on foot processes of astrocytes in the CNS2,3. In most series of NMO, more than half of cases are positive for AQP-4 antibody. In 2006, Wingerchuk et al.4 proposed the revised diagnostic criteria of NMO that incorporated AQP-4 antibody status. For definite NMO, the criteria require (A) ON, (B) TM and (C) at least two of three supportive criteria: (1) contiguous spinal cord lesion in the magnetic resonance imaging (MRI) extending over three vertebral segments; (2) brain MRI not meeting diagnostic criteria for multiple sclerosis (MS); (3) serum positivity for AQP-4 antibody.
NMO treatment has two main objectives: one is to control the inflammatory damage in acute attacks and the other one is a maintenance treatment to avoid relapses. The former is based on high dose intravenous corticosteroids and plasmapheresis5; the latter is based on low-dose corticosteroids and immunossupressants6,7. Additionally, there is evidence that AQP-4 antibody titers are reduced in patients without relapses under immunosuppressant treatment8,9. Although NMO attacks are related to severe disability, there are some evidences that NMO patients remain neurologically stable between them, without evidence of progressive deterioration like in MS1. Therefore, it is crucial that treatment is started as early as possible to avoid new relapses and further disability.
For this review, the English-language literature was systematically searched using Pubmed (National Library of Medicine) with the keywords neuromyelitis optica, and treatment was accessed on 20th July 2011, resulting in 394 articles. All articles available had the abstract analyzed and full article review was performed once considered relevant. Additional articles referenced in bibliographies from these articles were also reviewed. Case reports that revealed further insights into NMO, not identified in case series analyzed, were included in this review.
In this review, we used levels of evidence from the Agency for Health Care Policy and Research (also known as Agency for Healthcare Research and Policy)10 (Table 1) and the recommendation grades published for use in clinical guidelines from the American College of Chest Physicians Task Force (Table 2)11. We have classified the available studies in NMO accordingly and provided the recommendations for each treatment (Table 3).
Corticosteroids have been the mainstay treatment for NMO in both acute and maintenance phase. Methylprednisolone has been used since 1970 as a potent anti-inflammatory or immunosuppressant agent in the treatment of a variety of diseases including those of hematologic, allergic, inflammatory, neoplastic and autoimmune origin. In addition, it is also widely used in prevention and treatment of graft-versus-host disease following allogeneic bone marrow transplantation and acute spinal cord injury. Corticosteroids exert a wide array of physiologic effects including modulation of carbohydrate, protein and lipid metabolism, and maintenance of fluid and electrolyte homeostasis. Moreover, cardiovascular, immunologic, musculoskeletal, endocrine and neurologic physiologic functions are influenced by corticosteroids. Therefore, not only the positive effects can be observed, but also many adverse events can be originated from corticosteroids use. These adverse events can be seen acutely like mood/psychic changes, fluid retention with circulatory overload, hyperglycemia, hypokalemia and increased ocular pressure. Chronic corticosteroid use may promote other side effects like hypertension, hirsutism, Cushing's syndrome, hyperlipidemia, diabetes mellitus, gastrointestinal hemorrhage, aseptic necrosis and bone fractures.
The mechanism of action of corticosteroids is not completely understood, but many of their genomic functions originate from regulation of gene expression subsequent to binding specific intracellular receptors and translocation into the nucleus12. More recently, there have been observed evidences that corticosteroids in high doses, as used in high dose intravenous methylprednisolone (HIMP), have significant non-genomic effects, which may explain the rapid clinical response after infusion. These effects are probably mediated by a direct effect on cellular membranes and mitochondrial function, inducing a reduction of adenosine-5'-triphosphate production and promoting cellular apoptosis. Furthermore, HIMP also reduces the mitogen-induced increase of cytoplasmic calcium concentration and inhibits cation cycling across the plasma membrane with only a minimal effect on intracellular protein synthesis. The genomic and non-genomic effects may explain the positive effects of corticosteroids in NMO, inducing a reduction of inflammation, apoptosis of leukocytes, suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability.
Although the clinical efficacy of corticosteroids have been established in meta-analysis evaluating the treatment of neuroimmunological diseases13, only few clinical studies have rigorously investigated the efficacy and safety of corticosteroids in NMO. Consequently, the current practice of corticosteroids use in NMO is mainly based on few open-label studies and personal experience on treating other CNS autoimmune diseases.
The first open-label study in NMO evaluated the treatment of seven newly diagnosed NMO patients with long-term prednisone and azathioprine, with a follow-up every two months for at least 18 months6. Patients had no relapses during the observation period, and Expanded Disability Status Scale (EDSS) reduced from a mean of 8.2 at baseline to 4 at 18 months. A subsequent study reviewed related 25 patients with NMO who met the 1999 Wingerchuk's criteria and identified nine patients with long-term use of corticosteroid monotherapy7. The annual relapse rate was significantly lower under use of corticosteroids than the period without the drug (median 0.49 vs. 1.48). Still more interesting, the authors also observed that the odds ratio for the period with 10 mg/day or less was 8.71 if compared with 10 mg/day or over, suggesting that dose tapering below 10 mg/day for relapse prevention should be prescribed carefully, as it may be less than the required for the majority of patients for relapse prevention.
Another evidence that corticosteroids are useful to preserve normal nerve function in NMO is a retrospective study on NMO patients with optic neuritis relapse, which correlated the number of relapses, early corticosteroids intervention and a loss in retinal nerve fiber layer thickness (RNFLT)14. The overall RNFL was thinner in patients in the NMO group than in the MS (63.84 vs. 84.28 µm). The frequency of the ON relapses and the time for beginning the treatment with HIMP significantly affected the preservation of the RNFLT.
Plasmapheresis (PE) has been used as an alternative therapy for autoimmune diseases when HIMP is not effective. PE is an extracorporeal blood purification technique designed to remove antibodies, complement, cytokines and chemokines from the plasma. The quick removal of these substances may reduce further damage and interrupt the advancement of lesions faster than immunosuppressive agents, as autoantibodies can persist for several weeks in the circulation. It has been largely used for the treatment of thrombotic thrombocytopenic purpura, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, Waldenstrom macroglobulinemia and Guillain-Barré syndrome15. MS, NMO, acute disseminated encephalomyelitis, Lambert-Eaton myasthenic syndrome, paraproteinemic polyneuropathy and cryoglobulinemic polyneuropathy are some other neurological conditions sometimes treated with apheresis16. Due to the success in other immune mediate diseases, PE is used in NMO taking into consideration that there is evidence that NMO is an autoantibody-mediated disease with complement activation and PE has the potential to remove humoral immune products from systemic circulation17.
PE is often prescribed using at least five plasma exchange sessions to achieve a sufficient antibody removal. The rate of extravascular to intravascular equilibration is approximately one to two percent per hour, then five separate exchanges over seven to ten days are required to remove 90% of the total initial body immunoglobulin levels18. In order to be most effective, PE has to be associated with appropriate immunosuppressant therapy, avoiding new immunoglobulin production. If antibody production is not properly blocked, additional PE sessions may be required.
PE is an invasive therapeutic procedure and carries some complications. In NMO, it is usually performed using 5% albumin replacement, so complications from fresh frozen plasma infusion are avoided. Reported adverse effects have been hypotension, dyspnea/pulmonary edema due to fluid overload, citrate induced hypocalcaemia, coagulation abnormalities, infection and catheter related issues. As PE can also promote removal from serum of drugs such as azathioprine and cyclophosphamide; it is advisable that these drugs are administered following apheresis sessions19.
There is some evidence from some case series that PE is effective for acute relapse treatment in NMO patients who did not respond satisfactorily to HIMP5,17,20,21. Moreover, clinical response seems to be related to the early initiation of treatment20 and it may be observed quickly once PE sessions are started5. A review from the American Academy of Neurology about PE in neurological diseases indicates that there is Class II evidence that PE is probably effective to treat fulminant CNS diseases, including NMO22. However, the randomized study which provided such evidence included 22 patients with various CNS demyelinating diseases, like MS, ADEM, Marburg's disease, but only four patients with acute myelitis and two patients with NMO23. Other small case series have reported positive results with double membrane filtration plasmapheresis (instead of centrifugation technique)24 and PE used as rescue therapy 25.
The Guidelines on the use of therapeutic apheresis in clinical practice from the American Society for Apheresis published in 201026 considered that PE for NMO is accepted as second line therapy, as it may be helpful in recovery from acute attacks, although it does not prevent further relapses.
For long-term treatment, there is only a small case-series study (n=4) indicating that PE is effective not only for acute management, but also intermittent PE may be worthwhile for selected cases where long-term immunosuppressant treatment have failed21.
Azathioprine is a DNA synthesis inhibitor, as it is converted to a purine analogue, with interference in the purines synthesis (adenine and guanine). It inhibits the proliferation of cells, especially lymphocytes. The clinical effects are usually not seen before three to six months after initiation of therapy. It is a reasonably well-tolerated drug used for autoimmune diseases and organ transplantation either alone or in combination. It has been approved as adjunctive therapy in prevention of rejection of kidney transplants and for the management of active rheumatoid arthritis27. Additionally, many off-label uses have been reported, such as adjunct in prevention of solid organ transplants rejection, steroid-sparing agent for corticosteroid-dependent Crohn's disease and ulcerative colitis, dermatomyositis/polymyositis, MS and other autoimmune diseases.
Common adverse events reported with azathioprine include: fever, malaise, nausea, vomiting, leukopenia, thrombocytopenia, hepatoxicity, myalgia, and infections. It is reported a slight higher risk of developing cancer27. Therefore, periodic monitoring of patients with hematological (complete blood count with differential and platelets), liver function tests, bilirubin and continuous surveillance for clinical signs of cancer are required.
More recently, there is increasing evidence to evaluate thiopurine methyltransferase enzyme activity before initiating azathioprine therapy28. Thiopurine methyltransferase enzyme is involved in the metabolism of azathioprine and may determine the clinical response to thiopurines. Patients with intermediate or low thiopurine methyltransferase activity may be at risk for increased myelosuppression, sometimes life-threatening. Therefore, careful monitoring and dose adjustments may be required for these patients.
As previously described, the first study included seven newly diagnosed NMO patients with long-term combination of corticosteroids and azathioprine with positive results6. HIMP was given first for five days, followed by oral prednisone (1 mg/kg/day) for two months daily. At week three, patients started azathioprine (2 mg/kg/day). Two months later, patients began prednisone tapering very slowly until they have achieved a dose of 10 mg/day and azathioprine doses of 75 to 100 mg/day. Another study observed that suspension of azathioprine was followed by increase in AQP-4 antibody levels and clinical attacks in some patients, together with the interruption of corticosteroid in two patients or the maintenance of low-dose corticosteroid treatment (5 mg/day)9. A retrospective study with 36 Brazilian NMO patients analyzed those who used azathioprine alone or in combination with corticosteroids and provided similar findings of reduction in disability and relapse rates29. These results may indicate that combination therapy may be required in some patients. However, there are no multicenter controlled studies to provide class I efficacy evidence of this therapeutic regimen, and side effects may limit the use in some patients.
Rituximab is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells and it has the property to eliminate B cells selectively. Rituximab binds to the antigen on the cell surface, activating complement-dependent B cell cytotoxicity. It also binds to human Fc receptors, mediating cell killing through an antibody-dependent cellular toxicity. Rituximab is used in the treatment of many lymphomas, leukemias, transplant rejection and some autoimmune disorders. Besides the clinical studies with rituximab, another evidence that B cells and AQP-4 antibody are closely related to NMO pathogenesis is a case report of a Japanese NMO patient with hypogammaglobulinemia secondary to carbamazepine who reported no relapses during the lowered IgG levels, but who had no attacks relapsed later when the hypogammaglobulinemia resolved in association with the normalization of CD19+ cells30.
The first published open label study included eight patients in the USA, where rituximab was well tolerated, and positive response was observed in all patients with significant relapse reduction (2.6 relapse/patient/year to 0) and recovery of neurologic function measured by EDSS from 7.5 to 5.531. Rituximab was administered in four infusions of 375 mg/m2, administered once per week, and B cells were monitored with CD19 marker by flow cytometry. In the retreatment, the regimen used was 1,000 mg administered two weeks apart. However, one patient who did not receive the repeated course of rituximab when planned had an attack, indicating that treatment requires repeated infusions in order to CD19+ cells remain undetectable. A report of three Japanese NMO cases who received rituximab also observed positive results, with a remarkable reduction in the annualized relapse rate (from 5.0 in the pre-treatment to 0.6 in the post-treatment), but the decrease in EDSS was not so significant (from 8.7 in the pre-treatment to 8.0 post-treatment), maybe indicating that, although the drug was effective to control the inflammatory response, the irreversible damage had already been established32. Another study described two NMO cases treated with rituximab33. It was observed a good clinical response in one patient, but the other one have experienced relapses after the treatment, indicating that not all patients respond so well. A possible explanation for the occurrence of relapses following initiation of rituximab in some NMO patients is the transient increase in AQP-4 antibody titers and of B cell activating factor levels, which is observed for two weeks following the initial infusion34. Posterior reversible encephalopathy syndrome after rituximab infusion in NMO have been reported35, but this syndrome has been reported in NMO patients independent of rituximab36, so this may be a relapse related to rituximab initiation rather than a new treatment complication.
Another study retrospectively analyzed 25 NMO patients identified in seven centers from USA and Europe35. It was observed a marked reduction in the attacks and improvement in disability. The study had the two regimen of rituximab used in previous studies analyzed together (four infusions of 375 mg/m2, administered once per week, and 1,000 mg administered two weeks apart). The median follow-up was 19 months, and the mean post-treatment relapse rate dropped from 1.7 to 0. Disability has improved in 80% of patients, but two patients died during the study period, one due to a brainstem relapse and the other due to suspected septicemia. The study indicated a promising treatment option, but, like the traditional chemotherapies, it may expose patients to severe infections. Another retrospective study in the USA has also revealed that rituximab treatment was associated with reduction of relapses and stabilization or improvement of disability36.
A study with eight European patients evaluated the clinical response and AQP-4 antibody titers with different treatments, measured by a fluorescence immunoprecipitation assay using an extract from cells transfected with EGFP-tagged human AQP-4 M1 and M23 isoforms9. Four patients received rituximab and the reduction of CD19+ cells was correlated with a reduction of AQP-4 antibody titers and positive clinical response. The study also identified that relapses were preceded or paralleled by reoccurrence of CD19+ cells and an increase up to three-fold in the AQP-4 antibody. Another group has also confirmed clinical efficacy of rituximab in 10 NMO patients in Europe, but there was no correlation with AQP-4 antibody levels37.
Recently, the results of an open-label study with Korean NMO patients were reported with positive results38. Induction therapy was basically the same of previous studies, followed by maintenance therapy with repeated rituximab infusions (375 mg/m2, once) when the frequency of CD27+ memory B cells was more than 0.05% in peripheral blood. Interestingly, this approach reduced the number of infusions in the maintenance therapy, with a direct impact on treatment costs. Twenty-eight of 30 patients (93%) showed a marked reduction in the mean relapse rate from 2.4 to 0.3 while receiving rituximab over 24 months. Seventy percent of patients became relapse-free over 24 months, and disability either improved or stabilized in great majority of patients. One patient continued to have relapses despite rituximab treatment and was switched to mitoxantrone hydrochloride, and another patient had three relapses during treatment, but two relapses were associated with delayed retreatment. AQP-4 antibody levels declined significantly following treatment with rituximab, consistent with the clinical response and the effect on memory B cells. The most common infusion-related reactions, noted in 40% of patients during the first infusion, were transient hypotension and mild to moderate flu-like symptoms, such as a febrile sense, headache and skin rash. Less than half of patients experienced at least one infection episode during the study period, but there were no serious infection. There was no decline in serum total IgG titers, and no patient became seropositive for the JC virus over the 24 months.
Mitoxantrone hydrochloride is an anthracenedione used as an antineoplastic agent for prostate cancer and acute non-lymphocytic leukemia in adults. It has been approved for MS treatment, including secondary progressive MS, based on the evidence that it has reduced progression in MS patients with failure in other treatment regimens. It also reduces the clinical relapse rate and MRI outcomes in relapsing-remitting MS patients, and it is helpful on patients with clinical worsening conditions. However, the potential toxicity of this drug limits its use, and patients should be monitored periodically for cardiac, liver and kidney function39.
Considering the successful use in MS, mitoxantrone has been evaluated in NMO patients, but the case series have been very limited. In a study, five NMO patients received monthly intravenous infusions of mitoxantrone hydrochloride, 12 mg/m2, for six months, followed by three additional treatments every three months40. During the two years period of treatment, two patients had a relapse within the initial five months of treatment (one severe and one moderate), and improvement was seen clinically and on magnetic resonance images in four patients. One patient had a reversible decrease in cardiac ejection fraction. In another study, there were three patients who received mitoxantrone9. Unfortunately, the response was variable, from reduction of relapse rate in one patient to increased relapse rate in two patients.
Mycophenolate mofetil has been largely used for the treatment of several autoimmune diseases. It has a selective cytostatic effect on T and B lymphocytes. It is an inhibitor of inosine monophosphate dehydrogenase, which inhibits de novo guanosine nucleotide synthesis, required for proliferation of T and B lymphocytes. It has been used for prevention of organ transplants rejection and autoimmune diseases, like myasthenia gravis and systemic lupus erythematosus.
In 2006, a case report described a NMO patient successfully treated with mycophenolate mofetil 2 g/day who had no relapses over the following two years associated with clinical improvement41. Another study analyzed retrospectively 24 patients treated with mycophenolate mofetil (median dose of 2 g/day) with median treatment duration of 27 months. Patients had reduction in relapse rates (median annualized rate dropped from 1.28 to 0.09) and 91% of patients had stabilization or improvement of disability. In this study, six patients (25%) reported adverse events, which included headache, constipation, easy bruising, anxiety, hair loss, diarrhea and abdominal pain, and low white blood cell counts that required discontinuation42.
Cyclophosphamide is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent and has immunosuppressant activity. Cyclophosphamide is a prodrug that must be metabolized to active metabolites in the liver. It has been used in the treatment of many neoplasias and some autoimmune diseases, like severe rheumatoid disorders, Wegener's granulomatosis, myasthenia gravis, MS, systemic lupus erythematosus, autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura.
However, most studies are based on open-label studies or case series. In MS, the largest study from the Canadian Co-operative Multiple Sclerosis Study Group with 168 patients failed to demonstrate clinical efficacy of cyclophosphamide43. Another study has indicated some beneficial effects of cyclophosphamide in young MS patients, excluding those with primary progressive MS. In this study, the responsive patients received repeated cyclophosphamide infusions in a bimonthly basis after the induction phase44. Common adverse events of cyclophosphamide include: alopecia, fertility issues, nausea and vomiting, anorexia, diarrhea, mucositis, acute hemorrhagic cystitis or urinary fibrosis, anemia, leukopenia (dose-related with recovery from seven to ten days after cessation) and thrombocytopenia.
In NMO, there is scarce data, based mainly in case reports. The use of cyclophosphamide has been reported as effective in immunoablative doses (2,000 mg/day for 4 days) in a patient with NMO associated with refractory systemic lupus erythematosus after response failure with other treatments, like HIMP, intravenous immunoglobulin (IVIG) and rituximab45. However, another case report indicated a failure of monthly cyclophosphamide pulse (1,000 mg/m2) for six months, although NMO relapses were controlled with rituximab46.
The therapy using interferon beta has been used in MS treatment in routine practice for over 15 years. However, interferon beta is not currently recommended for NMO patients and there are some evidences that it also may be even harmful, increasing the relapse rates47. Other Japanese studies reported MS patients with good response to interferon beta therapy, compared with NMO patients who experienced increased relapse rate after interferon beta treatment48,49. Similarly, a series of 25 NMO patients from France were reported to experience relapses following treatment with interferon beta50. Additionally, there is a case report of a Caucasian NMO patient from United Kingdom51, suggesting that this deleterious response to interferon beta is probably not influenced by racial differences.
Eculizumab is a humanized monoclonal IgG antibody that binds to complement protein C5, preventing cleavage into C5a and C5b. Eculizumab inhibits the subsequent formation of terminal complex C5b-9 or membrane attack complex. It is currently under investigation for NMO in an open-label phase I clinical trial at a single center with 14 patients52. Eculizumab has already been shown to be effective in paroxysmal nocturnal hemoglobinuria53. Each patient will receive eculizumab at a dose of 600 mg each week for four weeks, then 900 mg at the fifth week, and 900 mg every two weeks for 48 weeks.
Anecdotal reports have been published using intravenous immunoglobulin54, glatiramer acetate55, but replication of these findings needs to be validated by other studies in a larger number of patients.
Other monoclonal antibodies used in MS treatment have been tried in NMO patients refractory to established treatments, like natalizumab, but NMO patients seem to not respond to these therapies (personal communication with Dr Anu Jacob, The Walton Centre, Liverpool UK, unpublished).
The use of corticosteroids and other immunosuppressant drugs for NMO treatment has been based on case reports or small series of cases rather than in double-blinded randomized studies. This does not mean that these drugs are not effective, but that higher levels of evidence of their effectiveness are still lacking. As NMO is a very severe and incapacitating CNS disorder, its treatment has to be decided on the basis of clinical judgment, physicians' experience, case series and extrapolation from management of other autoimmune conditions while clinical trials are not yet available to provide physicians with options grounded on stronger scientific support.
1. Wingerchuk DM, Hogancamp WF, O'Brien PC, Weinshenker BG. The clinical course of neuromyelitis optica (Devic's syndrome). Neurology 1999;53:1107-1114. [ Links ]
2. Lennon VA, Wingerchuk DM, Kryzer TJ, et al. A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 2004;364:2106-2112. [ Links ]
3. Pittock SJ, Weinshenker BG, Lucchinetti CF, Wingerchuk DM, Corboy JR, Lennon VA. Neuromyelitis optica brain lesions localized at sites of high aquaporin 4 expression. Arch Neurol 2006;63:964-968. [ Links ]
4. Wingerchuk DM, Lennon VA, Pittock SJ, Lucchinetti CF, Weinshenker BG. Revised diagnostic criteria for neuromyelitis optica. Neurology 2006;66:1485-1489. [ Links ]
5. Watanabe S, Nakashima I, Misu T, et al. Therapeutic efficacy of plasma exchange in NMO-IgG-positive patients with neuromyelitis optica. Mult Scler 2007;13:128-132. [ Links ]
6. Mandler RN, Ahmed W, Dencoff JE. Devic's neuromyelitis optica: a prospective study of seven patients treated with prednisone and azathioprine. Neurology 1998;51:1219-1220. [ Links ]
7. Watanabe S, Misu T, Miyazawa I, et al. Low-dose corticosteroids reduce relapses in neuromyelitis optica: a retrospective analysis. Mult Scler 2007;13:968-974. [ Links ]
8. Takahashi T, Fujihara K, Nakashima I, et al. Anti-aquaporin-4 antibody is involved in the pathogenesis of NMO: a study on antibody titre. Brain 2007;130:1235-1243. [ Links ]
9. Jarius S, Aboul-Enein F, Waters P, et al. Antibody to aquaporin-4 in the long-term course of neuromyelitis optica. Brain 2008;131:3072-3080. [ Links ]
10. United States Department of Health and Human Services. Agency for Health Care Policy and Research (AHCPR). Acute pain management: operative or medical procedures and trauma. Clinical practice guideline No 1, AHCPR publication No 92-0023. Rockville, MD: AHCPR; 1993. [ Links ]
11. Guyatt G, Gutterman D, Baumann MH, et al. Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians task force. Chest 2006;129:174-181. [ Links ]
12. Gold R, Buttgereit F, Toyka KV. Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol 2001;117:1-8. [ Links ]
13. Brusaferri F, Candelise L. Steroids for multiple sclerosis and optic neuritis: a meta-analysis of randomized controlled clinical trials. J Neurol 2000;247:435-442. [ Links ]
14. Nakamura M, Nakazawa T, Doi H, et al. Early high-dose intravenous methylprednisolone is effective in preserving retinal nerve fiber layer thickness in patients with neuromyelitis optica. Graefes Arch Clin Exp Ophthalmol 2010;248:1777-1785. [ Links ]
15. Clark WF, Rock GA, Buskard N, et al. Therapeutic plasma exchange: an update from the Canadian Apheresis Group. Ann Intern Med 1999;131:453-462. [ Links ]
16. Balogun RA, Kaplan A, Ward DM, et al. Clinical applications of therapeutic apheresis. J Clin Apher 2010;25:250-264. [ Links ]
17. Yoshida H, Ando A, Sho K, et al. Anti-aquaporin-4 antibody-positive optic neuritis treated with double-filtration plasmapheresis. J Ocul Pharmacol 2010;26:381-385. [ Links ]
18. Keller AJ, Urbaniak SJ. Intensive plasma exchange on the cell separator: effects on serum immunoglobulins and complement components. Br J Haematol 1978;38:531-540. [ Links ]
19. Sutton DM, Nair RC, Rock G. Complications of plasma exchange. Transfusion 1989;29:124-127. [ Links ]
20. Keegan M, Pineda AA, McClelland RL, Darby CH, Rodriguez M, Weinshenker BG. Plasma exchange for severe attacks of CNS demyelination: predictors of response. Neurology 2002;58:143-146. [ Links ]
21. Miyamoto K, Kusunoki S. Intermittent plasmapheresis prevents recurrence in neuromyelitis optica. Ther Apher Dial 2009;13:505-508. [ Links ]
22. Cortese I, Chaudhry V, So YT, Cantor F, Cornblath DR, Rae-Grant A. Evidence-based guideline update. Plasmapheresis in neurologic disorders: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2011;76:294-300. [ Links ]
23. Weinshenker BG, O'Brien PC, Petterson TM, et al. A randomized trial of plasma exchange in acute central nervous system inflammatory demyelinating disease. Ann Neurol 1999;46:878-886. [ Links ]
24. Munemoto M, Otaki Y, Kasama S, et al. Therapeutic efficacy of double filtration plasmapheresis in patients with anti-aquaporin-4 antibody-positive multiple sclerosis. J Clin Neurosci 2011;18:478-480. [ Links ]
25. Wang KC, Wang SJ, Lee CL, Chen SY, Tsai CP. The rescue effect of plasma exchange for neuromyelitis optica. J Clin Neurosci 2011;18:43-46. [ Links ]
26. Szczepiorkowski ZM, Winters JL, Bandarenko N, et al. Guidelines on the use of therapeutic apheresis in clinical practice-evidence-based approach from the Apheresis Applications Committee of the American Society for Apheresis. J Clin Apher 2010;25:83-177. [ Links ]
27. Carroll W, Fujihara K. Neuromyelitis optica. Curr Treat Options Neurol 2010;12:244-255. [ Links ]
28. Higgs JE, Payne K, Roberts C, Newman WG. Are patients with intermediate TPMT activity at increased risk of myelosuppression when taking thiopurine medications? Pharmacogenomics 2010;11:177-188. [ Links ]
29. Bichuetti DB, Lobato de Oliveira EM, Oliveira DM, Amorin de Souza N, Gabbai AA. Neuromyelitis optica treatment: analysis of 36 patients. Arch Neurol 2010;67:1131-1136. [ Links ]
30. Tanaka Y, Kimura K, Kawachi I, Inuzuka T. No relapse of neuromyelitis optica during drug-induced B-lymphopenia with hypogammaglobulinemia. Neurology 2010;75:1745-1747. [ Links ]
31. Cree BA, Lamb S, Morgan K, Chen A, Waubant E, Genain C. An open label study of the effects of rituximab in neuromyelitis optica. Neurology 2005;64:1270-1272. [ Links ]
32. Imamura H, Tanaka M, Kitagawa N, et al. Trial of rituximab in three patients with neuromyelitis optica. Rinsho Shinkeigaku 2009;49:457-462. [ Links ]
33. Capobianco M, Malucchi S, di Sapio A, et al. Variable responses to rituximab treatment in neuromyelitis optica (Devic's disease). Neurol Sci 2007;28:209-211. [ Links ]
34. Nakashima I, Takahashi T, Cree BA, et al. Transient increases in anti-aquaporin-4 antibody titers following rituximab treatment in neuromyelitis optica, in association with elevated serum BAFF levels. J Clin Neurosci 2011;18:997-998. [ Links ]
35. Jacob A, Weinshenker BG, Violich I, et al. Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol 2008;65:1443-1448. [ Links ]
36. Bedi GS, Brown AD, Delgado SR, Usmani N, Lam BL, Sheremata WA. Impact of rituximab on relapse rate and disability in neuromyelitis optica. Mult Scler 2011:Epub May 26. [ Links ]
37. Pellkofer HL, Krumbholz M, Berthele A, et al. Long-term follow-up of patients with neuromyelitis optica after repeated therapy with rituximab. Neurology 2011;76:1310-1315. [ Links ]
38. Kim S-H, Kim W, Li XF, Jung I-J, Kim HJ. Repeated treatment with rituximab based on the assessment of peripheral circulating memory B cells in patients with relapsing neuromyelitis optica over 2 years. Arch Neurol 2011:Epub July 11. [ Links ]
39. Goodin DS, Arnason BG, Coyle PK, Frohman EM, Paty DW. The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology 2003;61:1332-1338. [ Links ]
40. Weinstock-Guttman B, Ramanathan M, Lincoff N, et al. Study of mitoxantrone for the treatment of recurrent neuromyelitis optica (Devic disease). Arch Neurol 2006;63:957-963. [ Links ]
41. Falcini F, Trapani S, Ricci L, Resti M, Simonini G, de Martino M. Sustained improvement of a girl affected with Devic's disease over 2 years of mycophenolate mofetil treatment. Rheumatology 2006;45:913-915. [ Links ]
42. Jacob A, Matiello M, Weinshenker BG, et al. Treatment of neuromyelitis optica with mycophenolate mofetil: retrospective analysis of 24 patients. Arch Neurol 2009;66:1128-1133. [ Links ]
43. The Canadian cooperative trial of cyclophosphamide and plasma exchange in progressive multiple sclerosis. The Canadian Cooperative Multiple Sclerosis Study Group. Lancet 1991;337:441-446. [ Links ]
44. Weiner HL, Mackin GA, Orav EJ, et al. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993;43:910-918. [ Links ]
45. Mok CC, To CH, Mak A, Poon WL. Immunoablative cyclophosphamide for refractory lupus-related neuromyelitis optica. J Rheumatol 2008;35:172-174. [ Links ]
46. Birnbaum J, Kerr D. Optic neuritis and recurrent myelitis in a woman with systemic lupus erythematosus. Nat Clin Pract Rheumatol 2008;4:381-386. [ Links ]
47. Warabi Y, Matsumoto Y, Hayashi H. Interferon beta-1b exacerbates multiple sclerosis with severe optic nerve and spinal cord demyelination. J Neurol Sci 2007;252:57-61. [ Links ]
48. Shimizu Y, Fujihara K, Kubo S, et al. Therapeutic efficacy of interferon beta-1b in Japanese patients with optic-spinal multiple sclerosis. Tohoku J Exp Med 2011;223:211-214. [ Links ]
49. Uzawa A, Mori M, Hayakawa S, Masuda S, Kuwabara S. Different responses to interferon beta-1b treatment in patients with neuromyelitis optica and multiple sclerosis. Eur J Neurol 2010;
17:672-676. [ Links ]
50. Papeix C, Vidal JS, de Seze J, et al. Immunosuppressive therapy is more effective than interferon in neuromyelitis optica. Mult Scler 2007;13:256-259. [ Links ]
51. Palace J, Leite MI, Nairne A, Vincent A. Interferon beta treatment in neuromyelitis optica: increase in relapses and aquaporin 4 antibody titers. Arch Neurol 2010;67:1016-1017. [ Links ]
52. Mayo Clinic. An open label study of the effects of eculizumab in neuromyelitis optica (http://clinicaltrials.gov/ct2/show/NCT00904826). [ Links ]
53. Hillmen P, Young NS, Schubert J, et al. The complement inhibitor eculizumab in paroxysmal nocturnal hemoglobinuria. N Engl J Med 2006;355:1233-1243. [ Links ]
54. Bakker J, Metz L. Devic's neuromyelitis optica treated with intravenous gamma globulin (IVIG). Can J Neurol Sci 2004;31:265-267. [ Links ]
55. Bergamaschi R, Uggetti C, Tonietti S, Egitto MG, Cosi V. A case of relapsing neuromyelitis optica treated with glatiramer acetate. J Neurol 2003;250:359-361. [ Links ]
Douglas Sato
Department of Neurology
Tohoku University Graduate School of Medicine; 1-1, Seiryomachi, Aobaku
980-8574 Sendai Miyagi - Japan
E-mail: email@example.com
Conflict of interest:
There is no conflict of interest to declare.
Received 29 August 2011
Accepted 05 September 2011


text:
0 Items
All Products
Semi-Birth Stones
Sphatik Choice
Toggle navigation
1-21 Mukhi Rudraksha
Rare Rudraksha
Shakti Mala
Rudraksha Kawach
Siddhi Malas
Rudraksha Accessories for Luck
Java Rare Rudraksha
Rudraksha is a Sanskrit compound consisting of the name RUDRA (Hindu God Lord SHIVA) And Aksa (Eye).It is a large evergreen broad leaved tree whose seed is traditionally used for prayer beads in Hinduisum.Rudraksha seeds are covered by an outer shell of blue when fully ripe and turns black when dried, Rudraksha seed grows in three to four years. Rudraksha bead has got various number of natural lines on it which is called face or mukhi.Each face have got its own power .Rudraksha is found in Himalayan in Indonesia,Malaysia,India and mostly found in Nepal.Rudraksha is also used for treatment of various diseases in traditional Indian and Nepali Medicine ,In Nepal 2 to 1 face are available with some unique Rudraksha which has proved to solve many human life problems,
Ordinary Shaligrams
Special Shaligrams
Rare Collected Shaligrams
Shaligram representation of Lord VISHNU in the form of spherical,Usually black coloured stone found in the sacred river gandaki In Nepal. Also known as Holy Basil is closely associated with origins of Shila worship.According to the VISHNU had reunited with his wife,Also wanted to Lord Vishnu's consort.Once in anger Saraswati cursed laxmi.Saraswati's curse changed Lakshmi into a Tulsi plant and forced her live on earth forever.Vishnu,however,intervened and modified the curse,saying that Lakshmi would remain on the earth as Tulsi until the river Gandaki flowed from her body.In the meantime ,he would wait by the riverside in the form of a stone to take her back to his abode,This stone was the shaligram shila,which thus remained on earth as a representative of Vishnu.The shilla deities and the tulasi plant are thus always worshipped together as Vishnu and Lakshmi.
Semi-Birth Stones
Ruby ( Manik )
Emerald ( Panna )
Blue Sapphire ( Neelam )
Yellow Sapphire ( Pukhraj )
Coral ( Munga )
Pearl ( Moti )
Gomed ( Hessonite Garnet)
Cat's eye ( lehsunia )
Semi-Birth Stones
A birth stone is a gemstone or gem, also called a precious or semi-precious stone. Gemstones are chemical compositions of mineral, which in cut and polished forms, are used to make jewelry and rings by zodiac signs. Most gemstones are hard, but some soft minerals, like diamonds are very hard with hardnesses of 8-10 on the Mohs scale. Early civilizations, such as those in India and Nepal have attributed gemstones with magical properties and signs of the zodiac. Over time, astrologers have assigned gems of certain colors to the twelve signs of the zodiac to help people influence the planets in their favors. The stones are also worn by people based on their dates of birth.
Sphatik Choice
Sphatik Shivalinga & Nandi
Sphatik Sri Yantra(Meru)
Sphatik Ganesha
Sphatik Mala
Sphatik Choice
Spadikam or Sphatik (Quartz) also spelled as Spadikam is the mineral in the Earth's continental crust, after feldspar. It comprises one part silicon and two parts oxygen. Quartz belongs to the trigonal crystal system. The ideal crystal shape is a six-sided prism terminating with six-sided pyramids at each end. Sphatikam is the semi-precious gemstone. There are many different varieties of sphatikam. High quality quartz crystals are single-crystal silica with optical or electronic properties that make them suitable for hardstone carvings. The Hindu temples in South India use this semi-precious mineral for making Shiva Lingams. Sphatikam beads are made from translucent rose quartz and polished as beads. Each bead is about ten millimeters in diameter. It is a good conductor of heat. Hence people wear sphatikam jewelry (mala) to keep their body cool. Some other people claim that these beads have healing properties.
Sign In
» Doing pooja of
» Before Using Rudraksha
» View All
» Privacy Policy
» Terms Of Condition
» Shipping Policy
» Returns and Exchanges
Get to Know Us
» About Us
» Mission Statement
» Why Us?
» Contact
Let Us Help You
» Buyer Protection
» Wholesale Inquiry (B 2 B)
» FAQs
» Testimonials
Follow us on
Copyright © 2019 Rudra House, All rights reserved.


text:
Scrapbooks gone Digital! has a new free product sample for you. You can find it at the end of this post.
Courtesy of our wonderful designer: SgD DESIGNS . Below you can find some of her great products, or you can visit her SgD Store to see them all: SgD DESIGNS.
And here is the free product sample:
Alter Art Papers - Set of 12
by: SgD DESIGNS
Have a wonderful day!
Scrapbooks gone Digital! (SGDBLOG)


text:
What's the best managed pharma company?
The highlights: "Stealth Pharma" takes the Company of the Year honors, with newcomer Gilead Sciences posting a convincing win based on an impressive profit-to-sales ratio reinforced by strong management of its asset portfolio. In second place is Genentech, with an exclusive product franchise in oncology that continues to deliver premium prices. Meanwhile, the 2007 Company of the Year, Biogen-Idec, falls to third on the heels of a steep drop in one key metric: shareholder value.The lesson from this year's Audit is that it's how you grow that counts. And the organic growth that drives long term profitability is in scarce supply among the industry's standard bearers, with four of the top 10 companies in terms of sales—Pfizer, Sanofi-Aventis, GSK, and Merck—offering negative growth to shareholders. Still, with its enormous cash hoard, Big Pharma has the capacity to buy what it cannot build, and the current capital crunch in biotech has opened the door to acquisition of products, pipelines, and expertise at bargain prices—suggesting that the major players in the industry are slowly repositioning for better days ahead.
—William Looney, Editor-in-Chief
Pharmaceutical Executive's Eighth Annual Industry Audit analyzes the 2007–2008 performance of 27 publicly traded companies that file 10-K or 20-F reports on an annual basis with the US Securities and Exchange Commission. As in past years, the audit includes a wider array of performance metrics than found in the standard financial and accounting statements. Drawing on this larger set of sources allows for a more meaningful picture of performance, analyzing such key metrics as enterprise value in proportion to sales—a mission-critical driver of future prospects that focuses on profitability growth through product and process innovation. In addition to the 10-K and 20-F reports, the audit relies on proprietary and non-proprietary databases, as well as a broad array of secondary sources ranging from the business press to investor reports.
The key difference in this year's audit is an expansion in the number of companies examined, including those listed in Pharm Exec's separate survey of the 10 "stealth pharma" firms, last profiled in our June issue ("Stealth Pharma," June 2009). These include most of the emerging players in the biotech, orphan drugs and generics sectors, which were chosen for their high profile in the investment and scientific communities. Many are future leaders in the industry, with the scale, flexibility, and sophistication to fill the gaps exposed by the bureaucratization of Big Pharma brought on by two decades of consolidation.
The Pharma Industry Audit is also uniquely positioned to demonstrate whether a company's business strategy is actually enhancing shareholder value. If there's one metric that is the equivalent to food and water on a desert island, it's Enterprise Value. The market tempest of the past 18 months does carry a silver lining in that it forces investors to refocus on fundamentals. In the case of management, the measurement for success is simple: Do you create shareholder value or destroy it? For this reason, the audit gives highest priority to "Change in Enterprise Value" and "Enterprise Value to Sales." These numbers reflect a firm's market capitalization plus liabilities minus cash, or about what it would take to buy the firm on the open market. "Return on Assets" is another worthy exemplar of a commitment to long term profitability, and thus is given a significant weighting in the audit.
To accommodate the expanded sector profile, we've done some streamlining in the number of performance metrics, eliminating the earnings per share, price to earnings multiple, and R&D spend to sales indices. This allows a more focused examination of the indicators that matter most to investors.
With only eight metrics, the weighting formula of the audit has also been changed, with three of the metrics (covering value recognition and asset performance) weighted at 3 and the remaining five metrics weighted at 2. (The prior division of weights was set at 3, 5, and 7.) The audit retains the non-metric macro indicators on a scale and size that allow for viewing company performance in the context of overall industry trends.
Thus, determination of the final standing for each company relies entirely on the metrics—but not all metrics are equal. For instance, if a company places 10th out of 27 on a metric weighted at three, it receives (10 x 3) 30 points. Each company's points across all of the metrics are then totaled for a final score, with the company receiving the highest number of points overall designated as the Company of the Year.


text:
Free Shipping Australia Wide On Orders Over $50
8 Item(s)
View as:
Shopping Options
Please enter your email address below. You will receive a link to reset your password.
Back to Login
Checking "Remember Me" will let you access your shopping cart on this computer when you are logged out


text:
By throwing out most of the anti-Latino Arizona immigration law and neutering the rest, the Supreme Court struck a rare blow for fairness and justice. Let's hope this is the beginning of a streak.
By throwing out most of the anti-Latino Arizona immigration law and neutering the rest, the Supreme Court struck a rare blow for fairness and justice. Let's hope this is the beginning of a streak.
Let's also hope that Chief Justice John Roberts, who sided with the 5-3 majority in the Arizona case, likes the view from the liberals' end of the bench. They could use his vote on the health care reform ruling, expected to be announced today.
In a perfect world, the court would have definitively eliminated the most notorious section of the Arizona law: the requirement that police check the immigration status of anyone who is detained. Because of its chilling invocation of police-state tactics, this became known as the "papers, please" provision.
The court ruled that it is too soon to invalidate this part of the law, but it significantly narrowed the measure's scope and practically dared Arizona officials to step out of line.
"This opinion does not foreclose other pre-emption and constitutional challenges to the law as interpreted and applied after it goes into effect," the court wrote. Translation: We'll be watching closely.
Other parts of the law were less publicized but equally onerous and un-American. These provisions, happily, are now history.
Even more gratifying is the court's reinforcement of an obvious principle: The federal government has the responsibility for setting immigration policy, not the states. We do not need - and, thanks to this ruling, will not have - 50 sets of laws specifying who gets to live in this country and who doesn't.
The Arizona law sought to make it a state crime to fail to have proper immigration papers; in other words, failing to produce the right documents when asked could have subjected a person not just to deportation but to criminal penalties. The court ruled that this was pre-empted by federal law, which imposes no such sanctions.
Arizona's draconian statute also made it against the law for an undocumented immigrant to look for work. The court noted that existing federal law already addresses the employment issue but specifically puts the onus on employers, not workers.
It is "illegal for employers to knowingly hire, recruit, refer, or continue to employ unauthorized workers ... and requires employers to verify prospective employees' employment authorization status," the court said. "The correct instruction to draw ... is that Congress decided it would be inappropriate to impose criminal penalties on unauthorized employees."
And in a provision that, to my thinking, was even more oppressive than "papers, please," the Arizona statute gave police the authority to arrest anyone - without a warrant - suspected of some "public offense" that makes the person liable to deportation. The court recognized, quite logically, that this is a license for police to arrest suspected illegal immigrants indiscriminately, based solely on the possibility that they might be in the U.S. without the proper documents.
As the court noted in striking down this provision, "The result could be unnecessary harassment of some aliens (for instance, a veteran, college student, or someone assisting with a criminal investigation) whom federal officials determine should not be removed."
The majority opinion, written by Justice Anthony Kennedy, points out something that many who seek to participate in the immigration debate fail to understand: "As a general rule, it is not a crime for a removable alien to remain present in the United States."
That's right. It's not a crime for "illegal" immigrants to live and work here without the proper documents. By "here" I mean all 50 states. The United States is one country with one immigration policy, and the Supreme Court means to keep it this way.
That's why analysts who see this as a split ruling with "something for both sides" are wrong. The Obama administration won across the board on its central contention, which is that Arizona was trying to usurp a federal prerogative. This has huge implications for the other states, such as South Carolina and Georgia, that are also trying to design their own immigration policies.
There are political implications as well. Mitt Romney, who is struggling to reduce President Obama's huge lead among Latino voters, once referred to the Arizona law as "a model." Romney reacted to Monday's decision by reiterating that "each state has the duty and the right" to protect the nation's borders.
Actually, no. Romney should read the ruling.
Contact Washington Post columnist Eugene Robinson at email@example.com.


text:
- Home
- News
- Sports
- Opinion
- Obituaries
- Features
- Special Sections
- Classifieds
- Public Notices
Kenny and Terri Hasty and William and Tammy Scherer, all of Grandview, announced the engagement and approaching marriage of their children, Lindsey Hasty and Rick Scherer, both of Grandview.
The bride-elect is a 2003 graduate of South Spencer High School. She works at Harpenau Insurance.
Mr. Scherer is a 2003 graduate of South Spencer High School. He works at Waupaca Foundry in Tell City.
The wedding is planned for 2:30 p.m. Saturday, Nov. 13, 2010, in Lincoln Boyhood Memorial Park in Lincoln City.
A reception will be held at the Grandview Civic Center.
If you currently subscribe or have subscribed in the past to the Perry County News, then simply find your account number on your mailing label and enter it below.
Click the question mark below to see where your account ID appears on your mailing label.
|ZIP Code:


text:
Going green has become trendy. Politicians and celebrities are always talking about it, and most companies offer green versions of their products. But what exactly does it mean to go green?
Green living is a way of life in which people make choices that will benefit the environment and seek to do that which is best for the planet, including all the people who live on it. It involves being aware that life on this planet is now interconnected, and every choice we make affects others in ways we can't easily predict.
Green Eating: An Example of The Green Lifestyle
Advocates of the green lifestyle encourage eating organic foods as much as possible. Organic foods are grown or raised without chemicals or extra hormones; eating these natural foods helps you gain energy because you're not poisoning your body with chemicals or other unnatural elements. Thus, green eating is important for wellness.
However, there are many hidden benefits in going green with natural eating as well.
* Support of your local economy. A large part of green eating involves buying foods from local farmers as much as possible. Many cities have a farmer's market where you can buy fresh, organic vegetables for lower prices than you can get processed vegetables for in your supermarket. So by going green, you put money in local farmers' pockets and save money on food purchases.
* Save energy. Most supermarket food is imported from elsewhere in the world. This means that it has to be transported by air or ship. Once it reaches the United States, it's loaded onto trucks and driven to supermarkets. All this transportation has costs for the environment as well as for consumers – extra carbon emissions and greenhouse gases are released into the environment as a result of extra driving. In addition, buying green products saves on packaging, much of which is not biodegradable.
* Get more nutrients. Organic foods have more nutrients than processed food and are therefore better for your health. For example, organic milk contains more Omega-3 acids than processed milk.
* Promote organic farming. The more organic food you purchase, the more profit organic farmers make. This allows these farmers to stay in business. If organic farming becomes more profitable than making processed foods, businesses will offer more organic foods and organic farming will become the norm.
An eco-friendly lifestyle is about saving energy in everything you do. As the previous section demonstrated, your food choices save energy in ways you never imagined. Another core part of the going green lifestyle involves buying eco-friendly products, especially products that are made out of recycled parts. Making new things takes more energy than recycling.
Workers have to cut down trees or destroy other parts of the environment to make new products, then process those raw materials to make new products. This takes lots of energy. Recycling cuts out the step of getting new raw materials, which not only saves trees, water and other resources, but also saves energy because workers don't need to collect and process raw materials.
Sometimes it's not practical to buy recycled products. However, you can still save energy by buying products that use less raw materials. An alternative to buying new products is visiting second-hand stores. Second-hand stores allow you to buy products that were already created months or years ago at heavily discounted prices. So you won't be adding to the depletion of forests when you purchase items this way and you will be saving money too.
The ultimate energy-saving technique, of course, is to use renewable energy sources instead of non-renewable sources. About half of the people in the United States use electricity that is generated using traditional means such as burning coal. This is an example of a non-renewable energy source – eventually the planet will run out of coal – and in addition, burning coal sends toxins into the atmosphere.
The good news is that there are plenty of alternatives to non-renewable energy sources. Wind and solar powered generators can provide electricity without harming the environment or using non-renewable sources. In some areas, you might be able to generate your own electricity, and some electric companies offer credits for using renewable energy sources. Contact your utility company to find out what greener options it offers to customers.
Going green may seem complicated at first, but once you get used to it, it's an easier and healthier way to live. You can save energy and money in all sorts of ways you never considered. It's empowering to realize how much your choices affect this planet and people on it and to consciously make choices that will benefit all.
In this website, you will find information about the green and natural way of living and how to discover green wellness in your home, using natural products such as water filters, air purifiers, natural cleaning products, and organic beauty products. You will also find a great amount of info about organic food and organic gardening tips.
You can visit our ecology articles sector, where you can find many information about going green matters such as deforestation, global warming and the greenhouse effect. Also don't forget to check on our green living friends. You will definitely find very useful and quality information there.
Consider buying grand prairie texas apartments : it will definitely change your life for better. Find decent variants here: https://www.enclaveatmiralagos.com/


text:
Support foreign language acquisition with Skills for Success: Building Spanish Vocabulary for students in all grades.
This 128-page resource book is designed to help introduce Spanish in your classroom, while emphasizing vocabulary development. It helps students practice beginning Spanish vocabulary and build awareness of Hispanic culture.
This book includes these ways to teach and practice Spanish:
- game ideas with easy-to-follow instructions
- reproducible game cards with Spanish vocabulary words and their English translations
- more than 350 Spanish vocabulary cards
- a pronunciation guide
- an answer key
- Answer Key
Crayola® Concepts, Set of all 6 books (Spanish)
Vibrant photos and engaging text present early childhood concepts with a splash of Crayola color. Each title encourages readers to create art inspired by the world around them. A special feature shows the Crayola colors that appear in photos throughout the book.
Use these activities on their own or in addition to any Spanish program!
The exercises in this 128-page elementary Spanish resource book are presented in a range of formats designed to help students acquire basic Spanish vocabulary.
Vocabulary lists, reproducible storybooks, pronunciation key, and an answer key are all included.
- Answer Key
Support language acquisition using Skills for Success: Spanish for grades 6–12.
Middle school and high school students can use the activities in this 128-page book on their own or in addition to any Spanish program.
The exercises in this resource book are presented in a range of formats that help students acquire basic Spanish vocabulary. The book includes vocabulary lists, reproducible storybooks, a pronunciation key, and an answer key.
- Answer Key


text: It's time to amp up your team swag for March Madness with UCLA Bruins Basketball Hats from the shop at CollegeBasketballStore.com. Our Bruins Hoops Caps come in a variety of styles from great brands like Top of the World, Nike and New Era. Find essential UCLA Basketball Caps in snapback, adjustable and fitted styles in our collection. Check out the College Basketball Store for the latest designs for this basketball season. Whether you're interested in a casual retro style like a Trucker Hat or a sleek new basketball Snapback, CollegeBasketballStore.com will keep you decked out in new UCLA March Madness Hats throughout the NCAA Tournament.


text:
Asphalt Paver:with a rented paver machine Lay asphalt quickly
For demolish the old, especiallythe concrete.
Rent a walk-behind compactor for building a solid base.
Use a rented concrete buggy to move material from one place to another site.
Clean, smooth and level concrete with rented concrete tools.
Rent a Concrete trailer to mix and Transfer concrete.
Create a curb, or gunite a pool with the help of rented concrete tools.
Keep the traffic flowing during construction with rented road plates and trench boxes.
When the time arrives to cut or remove concrete, renting a tough, concrete saw makes the concrete work easy
Rent a shot blaster to clean concrete or metal surfaces
Create a temporary road or work platform with rented mats and roadways.
Keep traffic flowing safely with rented barricades, cones and signs.
Rent attachments to make your backhoe more efficient.
A rented backhoe is the perfect tool for your work
Rent a walk-behind compactor for building a solid base.
for Moving material very quickly rent a dozer.
Dig a trench, foundation or complete a demolition with a rented excavator.
Renting ground-heating equipment will extend your season by thawing frozen ground for excavation.
Rent a mini skid-steer for small projects.
Rent a skid-steer loader to easily complete small jobs in tight land.
Rent a trencher to easily bury pipe or cable either in farm or in landscape
Alert others and stay safe with rented arrow boards and message boards.
Keep traffic flowing safely with rented barricades, cones and signs.
Need to move equipment or people around your work site? Rent a utility vehicle.
It make simple of many different types of overhead jobs
For materials Handling and warehouse equipment moving Rent Forklifts
Rent a rough-terrain forklift for outdoor or off-road material handling.
When a forklift is too small and a crane is too big, rent a telescopic handler.
Need to move equipment or people around your work site? Rent a utility vehicle.
You can rent air compressors of different sizes according your needs
Rented generators can offer a source of power with portability
Rent an air compressor to increase work capability.
Are you looking for Construction & Industrial Equipment on rent in Wheaton, il? our rental member stores would meet all your general equipment rental needs in Wheaton, IL.
Our member Construction equipment rental stores provide best in quality equipment rentals and tools on rent at best affordable prices in Wheaton, IL.
ARACHICAGOLND is an organization of General Equipment, Tools and Equipment Rentals member Stores in Wheaton and Chicagoland area.
For Construction Equipment on Rent in Wheaton, IL or other General Equipment, Tools and Party/Event Rentals in Wheaton, IL our rental members' stores are here to help you out.
To find Rental Stores in Wheaton, IL, ARACHICAGOLAND is here to help you out.


text:
I would like to publicly apologize to Galeltic for making fun of his engish. My words have been a huge mistake, and I stand here asking for his forgiveness.
In another post, I made fun of the way Galeltic spoke (wrote). Some information has come to my attention that significantly changes how I view the way he speaks.
I never ment to be un-sporty, and I now stand with my foot in my mouth.
Please accept my apology.


text:
Pictures of Katie Holmes on the February Cover of Elle Magazine 2011-01-05 15:15:00
Sultry Katie Holmes Talks Suri's Shopping Style and the Complexity of Portraying Jackie O
Sultry Katie Holmes Talks Suri's Shopping Style and the Complexity of Portraying Jackie O
Katie Holmes strikes a few flirtatious and sexy poses on the February cover of Elle. She's been ramping up for a busy 2011, which will include juggling her fashion line, traveling with Tom Cruise and their family, starring in two films, and portraying Jackie O in the History Channel's upcoming miniseries The Kennedys. Inside the magazine she shares what it's like to play the role of an American icon and how she prepared herself emotionally for the role. Of course, an interview with the actress wouldn't be complete without a few anecdotal stories about her fashionable daughter, Suri. Here's more:
- On working hard to perfect her portrayal of Jacqueline Kennedy: "I worked as hard as I could, because I loved her. On set there was this feeling that we had to create something very special, because these people were very special."
- On playing such a complex role: "[The Kennedys] were like movie stars. There was such a professionalism to their public image."
- On designing for her clothing line, Holmes & Yang: "I have such an appreciation for the fine details and the amount of work it takes. I really appreciate clothing and designers so much more. It's made shopping even better."
- On Suri's shopping style: "The other day we came out of a store, and she said, 'I want to go there,' pointing at another store quite a distance away. In that store was the dress that she wanted. I said, 'Wow, Suri. You're something. You picked that out from a football field away.'"
- On getting fashion advice from Suri: "She'll really tell me [what she thinks]. Like today I'm wearing brown suede pants, and she said, 'I don't like your pants.' But then she'll say, 'You've got to wear these shoes.' Or 'That's so pretty, Mom. Wear that.' She's got a great eye."


text:
Main Content
For the Horde! This gruff shout is a veritable mantra among the Tauren, Orcs, Trolls, and Undead. Make Thrall proud and wear this shirt as a token of courage, power, and defiance. Tauren are advised to take extreme care not to spear this shirt on their horns when applying.


text:
Just a few years ago amidst a cruel drought many were predicting the end of irrigated dairy farming in the Murray-Darling Basin.
Farmers left the industry in droves, cows were sold, land left abandoned and close to half the region's milk production was lost.
But almost as quickly as the hard times hit, things are turning around and many are describing the comeback as the stuff of legend.
Murray Dairy is the industry group that provides direction and research for farmers in a large part of northern Victoria and southern New South Wales.
Chairman, Malcolm Holm is a dairy farmer at Blighty between Finley and Deniliquin in southern New South Wales.
"We hit 3.2 billion litres (of milk produced) across Murray Dairy and fell down to 1.86 billion litres (during the drought) and now we are back at 2.25 billion litres.
"With the seasonal conditions around us, we anticipate growth to keep happening."
The industry has been helped by the farmers that survived the drought expanding and new entrants coming to northern Victoria to dairy.
One of those is Andrew Wilson who four years ago at the height of the drought decided to do the unthinkable and start a dairy farm in northern Victoria.
"I sort of got in when everyone was getting out, which is what they say you should do but no one ever does.
"The farm I have taken over was a beef farm, it was originally a dairy that went to beef (during the drought), so I have turned it back into a dairy.
"Three neighbours have now also done the same."
Since starting Andrew has developed a strong, profitable dairy business that milks 200 cows.
He has been so successful that he can afford to build a new house which he says will keep him focussed on dairying, 'for another two or three years.'
The revitalisation of dairy in the Murray Dairy region doesn't necessarily mean factories that were closed or downsized will automatically reopen.
"To some extent that will be some time off," believes John Droppert from Dairy Australia.
"We did have the infrastructure to process 11 billion litres of milk in this country and we are still only up to 9.5 (billion litres).
"You are probably likely to see new investment rather than reopening of old plants because we are getting down the track a bit and it is old technology.
"I guess the sort of products they were producing aren't necessarily the ones that will be demanded in this day in age."
As other areas of the country deal with their own problems of drought, expensive land and competition from other agricultural industries, the Murray Dairy region is picking up the slack.
After coming through their own problems, Malcolm Holm believes a new breed of dairy farmer has emerged in the area that can compete on a global scale.
"I think essentially, anybody that's gone through the drought in the last decade, I reckon we can just about put them anywhere in the world and they could make a go of it.
"We have been able to cope with a whole range of situations."


text:
Member Since 2013Ask Question
Rock & Heavy Metal
This item is handmade
Material: PU leather, Alloy
Item ships from: China
Ready to ship in 1-3 days
Calculate shipping cost to your country
This store does not ship to these countries: Afghanistan, Albania, Algeria, American Samoa, Andorra, Angola, Anguilla, Antarctica, Antigua and Barbuda, Armenia, Aruba, Azerbaijan, Bahamas, Barbados, Belarus, Belize, Benin, Bermuda, Bhutan, Bolivia, Bosnia and Herzegovina, Botswana, Bouvet Island, British Indian Ocean Territory, Burkina Faso, Burundi, Cambodia, Cameroon, Cap Verde, Cayman Islands, Central African Republic, Chad, Christmas Island, Cocos (Keeling) Islands, Comoros, Congo, Congo, The Democratic Republic of the, Cook Islands, Costa Rica, Cuba, Cyprus, Djibouti, Dominica, Dominican Republic, Ecuador, Egypt, El Salvador, Equatorial Guinea, Eritrea, Estonia, Ethiopia, Falkland Islands (Malvina), Faroe Islands, French Guiana, French Polynesia, French Southern Territories, Gabon, Gambia, Georgia, Ghana, Gibraltar, Greenland, Grenada, Guadeloupe, Guam, Guatemala, Guernsey, Guinea, Guinea-Bissau, Guyana, Haiti, Holy See (City Vatican State), Honduras, Hong Kong, Iran, Islamic Republic of, Iraq, Isle of Man, Jersey, Kenya, Kiribati, Lebanon, Lesotho, Liberia, Libyan Arab Jamahiriya, Macau, Macedonia, The Former Yugoslav Republic of, Madagascar, Malawi, Maldives, Mali, Malta, Marshall Islands, Martinique, Mauritania, Mauritius, Mayotte, Micronesia, Federal State of, Moldova, Republic of, Montenegro, Montserrat, Morocco, Mozambique, Namibia, Nauru, New Caledonia, Nicaragua, Niger, Niue, Norfolk Island, Northern Mariana Islands, Palau, Palestinian Territory, Occupied, Panama, Papua New Guinea, Pitcairn, Rwanda, Saint Barth, Saint Helena, Ascension and Tristan da Cunha, Saint Kitts and Nevis, Saint Lucia, Saint Pierre and Miquelon, Saint Vincent and the Grenadines, Samoa, San Marino, Sao Tome and Principe, Senegal, Serbia, Seychelles, Sierra Leone, Solomon Islands, Somalia, South Georgia and the South Sandwich Islands, Sudan, Suriname, Svalbard and Jan Mayen, Syrian Arab Republic, Tanzania, Togo, Tokelau, Tonga, Trinidad and Tobago, Turks and Caicos Islands, Tuvalu, Uganda, United States Minor Outlying Islands, Vanuatu, Virgin Islands (British), Virgin Islands (USA), Wallis and Futuna Islands, Western Sahara, Yemen, Zambia, Zimbabwe.
Contact store to request shipping to your country.
Exceptions may apply. View policy


text:
One Response to Algo Trading Basics
Leave a Reply Cancel reply
- Paper Airplane Exercise
- 25 Tips for Writing Business Emails
- 20 Tips for building Algorithmic Trading Application
- Launching New Product
- Algo Trading Basics
- Role of Parents in Indian Startups
- From the Co-Founder's Desk
- Startup kick
- Effective vimdiff
- "I" can make a difference
- Must have tools for a blog
- Reducing Database Latency
- Startup Specialist
- 10 qualities tested in interviews
- Ideas on Low Latency Software
- Gym Ball for back ache
- Hiring In Tech-Startup: 10 Tips on Accelerating
- 10 tools C C++ Linux Programmer must know
- Linux and Windows dual boot : BIOS UEFI/EFI
- Startup Culture: Labour Room
- BOOST multi-threading for C++
- 7 thoughts : Corporate Job To Entrepreneurship
- Linux Multi-threading : FIFOs or Named Pipes
- Linux GUI on windows
- Mistakes in tech-startup
- Charm of switching domains
- World's best universities giving free online courses: coursera.org
- Agile – Scrum software development
- screen utility
- Why work in a startup?
- Hiring in Tech-Startup: 10 Tips on Quality
ImportantThe content published has nothing to with any organization or individual the author has been associated with at any point. Content posted here should not be re-published anywhere without permission.


text:
Carraig Donn
There is a wide range of products giving a full flavor of this collection. Browse shoulder bags, slipper socks, shamrock blankets, cardigans, sweaters, mittens, gloves, and so much more all in one place. Carraig Donn knitwear is steeped in heritage because of its Irish origins and ongoing development as a brand and quality product since the early sixties. ShamrockGift are proud suppliers of this authentic brand. Their products are designed and made in Ireland. Look out for some of the handmade items that make an extra special gift and ensure a unique purchase for those wishing to break away from the expected. All of our Carraig Donn pieces come with free gift wrapping. Most orders before 3pm ship the same day and orders over $100 are shipped for free. Additionally, 30-Day no hassle returns or exchanges. If you are looking for a taste of Ireland's finest this range comes from the heart of its heritage. "Go raibh maith agat!" – Thank you!
Items 1-18 of 114
- As low as $98.99
- As low as $68.99
- As low as $92.99
- As low as $95.80
- As low as $98.50
- As low as $109.50
- As low as $89.95
- As low as $79.99
- As low as $94.50
- Out of stock
- As low as $199.99
- Out of stock
- As low as $42.99
- As low as $32.75
- As low as $22.95
- Out of stock
- As low as $59.99
- As low as $59.99


text:
Kit Linton necesitaba un nuevo diseño de logotipo y lanzó un concurso de diseño en 99designs.
Un ganador ha sido elegido entre 160 diseños de 59 diseñadores freelance.
Geotto.com is an online portal that provides a broad array of information on outdoor activities. Specifically, geotto is being launched to fill a gap in the online community for access to detailed, user-driven content and reviews for local adventures. 'Local' is the key word here - whereas there are plenty of commercially oriented sites on the web to help a user buy a vacation package, there is very little related to simply finding a fun local activity for a weekend afternoon. Geotto will provide context-sensitive data on a variety of activities ranging from mountain biking to paddle sports, camping and fishing, triathlons and adventure racing (and many more) based on a users locale and interests. Geotto is designed to be customizable for the repeat visitor, allowing them to create their own profiles, post video, pictures and reviews of adventures they have enjoyed. Geotto.com will be piloting in North Carolina initially and will then move to service a national audience in the United States. Initially, the geotto business model will be based on online advertising of outdoor equipment and activities including retailers, outdoor equipment manufacturers and outfitters. The culture at geotto.com is one that cares about the promotion of local activities and values. We will perform mostly grass-roots marketing by taking part in and sponsoring local activities and events.
Primary Audience:
Young professionals aged 25-45 with discretionary income, many of whom are parents of young children. They enjoy outdoor activities but have a hard time squeezing them into their busy schedules - hence the 'local' angle of the site. These users have less familiarity with social collaboration sites and so may drive less content but are really the primary targets of our advertisers.
Primary Audience:
Active men and women aged 16-25 who enjoy taking part in outdoor activities on a regular basis but who are also very comfortable with online collaboration and social networking technologies (e.g. Facebook). Many of these users will be college-aged or entering the early years of professional life. These are the content drivers for the site.
Other Audiences:
While the above represent the main targets, it is also important to have a brand that is attractive to two other sets of users: First, retirees aged 60-70 are big drivers of outdoor dollars. These are really the set of people escaping cross-country in recreational vehicles or just interested in finding activities to fill their time. They have some familiarity with technology but are unlikely to contribute content. Second, men aged 25-45 who enjoy taking part in outdoor activities like fishing and hunting also represent a huge population and a significant portion of outdoor dollars spent.
Primary Requirements:
1.) the geotto logo must influence the viewer to pronounce the name as 'gee-oh-toe' and not 'gee-ah-toe'
2.) the logo must provoke a sense of adventure and of the outdoors
Other Requirements:
3.) the logo should be simple with clean lines
4.) any imagery used in the logo should be abstract
5.) 'geo' in the name is meant to represent 'earth', as in the words geology or geography. to this end, the logo should not look too 'techy'
6.) the logo should appeal to each of the audiences above, since this is quite diverse simpler is better
7.) the logo should be compact so that it can be readable in an iPhone icon
8.) I have been thinking about charcoal and forest green colors for the logo (not a hard requirement)
Descubre cómo funciona un concurso de diseño u obtén más información sobre nuestros servicios de diseño de logo.


text:
Once again the Refugee Convention has become the whipping post for political discontent about boat people and ''border protection''. The Prime Minister thinks it is outdated and queries its ''effectiveness'', echoing the concerns of Philip Ruddock under the Howard government. Both the Prime Minister and shadow immigration minister also believe that it is interpreted too generously in Australia.
Already the government has directed refugee decision makers to consider the government's views on the safety of countries of origin, politicising and compromising decisions. It also complains that ''economic migrants'' are abusing the system. Policy changes are afoot, though the devil will be in the detail. There is a grave risk that further changes will undermine, not strengthen, refugee protection.
The Refugee Convention is certainly old, originally adopted in 1951 to deal only with the postwar refugee crisis in Europe, and amended in 1967 to cover refugees globally. It is true that the convention does not cover every conceivable aspect of the world's refugee problems. It does not address the different ways that refugees move, including through transit countries such as Indonesia, or the different types of refugee populations, such as those ''warehoused'' for protracted periods in camps.
But the convention's limits are not a good reason to throw out the baby with the bathwater. The convention's essential principles remain eternally valid, and precious, including that governments must not return anyone to persecution. Any retreat by Australia from that principle would have catastrophic consequences for human safety. It would also signal to other countries that refugee protection is no longer an important global value.
The convention does not protect economic migrants. Australian decision makers have never interpreted it to do so, though there are other powerful moral reasons for helping the world's poor. The majority of ''boat people'' are found to be refugees because they are refugees. If they are not, the convention allows them to be sent home. Our refugee decision makers are skilled and should be respected, not denigrated by politicians.
The convention was never intended to be the last word on refugees. Countries have always had the option of pursuing additional bilateral or regional co-operation to address refugee problems. The convention does not impede such efforts, as long as people are not returned to persecution. Such measures are the only way to resolve the current difficulties, in a region where most Asian countries are not parties to the convention. It is reasonable to expect other countries in the region to assist in managing the common challenge of refugees.
The convention is also a flexible instrument, leaving many issues to national discretion, including refugee determination processes. Indeed, one of its flaws is that it concedes too much to states, and does not demand enough of them in protecting refugees.
Realistically, Australian politicians are dreaming if they think they can convince other countries to amend the convention. There is no political appetite for it internationally.
Many countries would find it laughable that an astonishingly rich and underpopulated country like Australia would seek to amend the convention in response to its extremely modest refugee flows.
Many poor and overpopulated countries are staggering under the weight of huge refugee populations, without seeking the concessions Australia demands. Any effort to amend the convention would risk undermining, not strengthening, refugee protection.
The problem is not the convention or its interpretation. The problem is our politics. In recent decades, governments have tried every trick in the book to deter refugees, including detention, restricting the refugee definition, ''safe country'' provisions, limiting review by tribunals and courts, excising territory and offshore processing, naval push-backs, and temporary protection.
Yet, still the refugees come. This should tell us something about the refugee experience. If the risk of drowning at sea is no deterrent, nothing short of eliminating refugee status altogether will stop refugees coming. Refugees know the risks, but make the calculated decision that the chance of a new, safe life is worth the danger at sea. There is no orderly ''queue'' to speak of that they can be expected to wait in so as to acquire ''no advantage''.
If the risk of drowning at sea is no deterrent, nothing short of eliminating refugee status altogether will stop refugees coming.
We are not facing a ''national emergency'' as suggested by Tony Abbott. We are merely facing the real world, the awful everyday experience of millions of refugees, which a sheltered Australia tries so desperately to insulate itself from. Talk of stopping the boats is a proxy for stopping more refugees coming. If this is our collective policy choice, we should be honest about it and stop speaking in euphemisms.
If not, then our policies should save life at sea while also protecting refugees. The way to do this is not to shunt our refugee problem onto our neighbours, where refugees are not safe from return to persecution, and where those countries have vast problems of their own. Currently, refugees in Indonesia wait for years in detention, or penniless and illegally in the community, making getting on boats very attractive.
The solution is to support UNHCR and regional governments to swiftly process refugees and provide them with real solutions. Then they will have no need to get on boats. It would be cheaper, more effective, and more humane than the current fiasco. Australia already funds much of UNHCR's operations in Indonesia.
We cannot simply blame our politicians or the media for turning against refugees. People get the politicians they deserve. Politicians naturally pander to electorally decisive prejudices. The average Australian enjoys extraordinary fortune by world standards, but privilege has bred concern for ourselves not others. In the internet age, it would take little effort for Australians to educate themselves about the real state of the world's refugees. Not enough could be bothered to do so, yet still feel entitled to express an opinion on the subject.
We should expect more of ourselves. We should not become a hard country of dry souls.
Ben Saul is professor of international law at the University of Sydney.