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After Tivoli – A Different Take
by tdomf_5a532 / 5 Comments
After pressure was brought to bear by the US on extraditing Christopher 'Dudus' Coke and with the disclosure on his role in the related Manatt Phelpa & Phillips imbroglio, Bruce Golding decided to do something to salvage what little, if any, political capital he still had left. He decided to OK the extradition request and asked his Justice Minister/Attorney General, Dorothy Lightbourne to sign of on it. He also decided to have the security forces go into Tivoli Gardens to execute the warrant for Coke's arrest. Folks in Tivoli Gardens, including Coke, knew what was coming and were supposedly prepared for the worst.
Sometimes you have occasions where prophesy becomes self-fulfilling. Folks in Tivoli feared the worst and by their actions they fulfilled their worst fears. The security forces entered the community looking to apprehend Coke but they were met by force from 'defenders of Coke' and from folks who supposedly have Tivoli Gardens' 'best' interests in mind.
Those with Tivoli's supposed best interests in mind are/were the ones who supposedly confiscated people's cell phones and who supposedly threatened those who wanted to heed the security forces advice to leave. These are the 'patriots' of Tivoli. I always thought that true patriots were those who put the well-being of their community and country ahead of their own individual concerns in times of national crises and not vice versa. I guess that concept has been totally lost on me. To borrow a quote from the musician Sting, 'If you love someone, set them free.'
The loss of 73 civilian lives in Tivoli Gardens is sad and regrettable but it was to be expected. For those who are crying 'massacre' and 'blood bath' and are otherwise being overly dramatic in their description of events in, I say, 'Please, enough already.'
History is replete with instances of folks and states fighting tyranny, whether from outside or within, to gain freedom and innocent blood being shed in the cause. This does not excuse any excesses that might have been engaged in by members of the security forces but neither should all the blame be laid at their feet.
For those human rights organizations in and outside Jamaica who have been calling for inquiries as to what really went down in Tivoli Gardens involving the security forces, please be equally vociferous in wanting to find out why the criminals in that enclave refused to let those who wanted to leave before these events, were not allowed to do so. The implication, no matter how subtly or sophisticatedly put, is very, very hard to swallow: that everyone in Tivoli was so enamored and enthralled with Coke and his minions.
While human rights entities and other 'contrarian' voices do serve as the conscience of democracies, there is, in times of crises, the impression that they are quick to castigate and criticize the state in its response to armed violence being perpetrated against it by organized groups/entities while they are seemingly reluctant to be as vocal/vociferous in their criticism(s) against criminals/terrorists.
Violence, when perpetrated by either the state or by criminals in order to achieve certain aims/goals/objectives, against the helpless, innocent and vulnerable is a human rights violation. The perpetrators must be called out without fear or favor, regardless of who they are and their political/philosophical leanings.
While it should not be expected that in a democracy the media should always be in lockstep with every action taken by the government of the day, it is incumbent upon them to not just report matters in such a way as to prejudice folks against one side or another that could further exacerbate a bad situation and make it worse.
When I read a column where the author is claiming that the security forces massacred seemingly innocent civilians in Tivoli gardens, I asked myself what does he know that folks in Jamaica don't. This even more so when he stated that he was in the northeast US when the security forces made their incursion into Tivoli. Then you have one other columnist, based in the US and also writing in the same newspaper as the aforementioned, who said that Coke was not the real enemy of Jamaica.
Yes, we don't want Op-Ed pieces and columns in newspapers and periodicals to all be expressing the same opinions and variety/diversity in terms of opinions and their proponents should be sought out. That said, words and their authors/speakers can have an effect especially when they are published in widely read news outlets or spoken over the (public) airwaves.
In a democracy, one can disagree with the government and should not have to suffer for said disagreement. What should not be the case, however, is that in disagreeing with the state one does not resort to language that can encourage folks to take up arms against the state or resort to violence against the state to get its attention.
When former prime minister and member of parliament Edward Seaga, who created the Tivoli Gardens housing development goes on TV and questions Bruce Golding's legitimacy as PM and whether or not he has full control over the security forces, that is wrong. When Ken Chaplin writes in his Observer column that the security forces massacred folks in Tivoli, that is wrong, especially when he was not even in Jamaica when stuff was going down.
When Mervin Stoddart wrote in his Observer column that Coke is not the real enemy of Jamaica, I'm left to question what alternate universe is he living in or if he has been smoking something funny. When someone and his minions would seek to violently resist a duly and fairly elected government from carrying out its legal duties in any part of the country, that is wrong – especially when there is a sound legal basis for carrying out said duty.
The question here is not whether there should be a variety of opinions on the Op-Ed pages (there should be) but for folks to exercise discretion and exhibit some degree of intelligence. After a while, it gets rather stale when you're always blaming 'whitey' for all the problems black folks face.
To folks like Ian Boyne, stop with the seeming incessant praises of Bruce's excellence of elocution on the issues and concentrate more on his excellence of execution (or lack thereof) of his job as leader of Jamaica.
The point here is that those who are in a position to influence events in Jamaica need to do a better job of doing this. We want and/or should see to it that in a democracy the government's feet is held to the fire and that any action(s) undertaken should be to the benefit of all in society and not just for the well-heeled, well-connected and/or wealthy.
In a democracy, we want human rights organizations to do more than just focus on any human and civil rights violations committed by the state and to speak out just as forcefully and vociferously against those committed by criminals/terrorists against citizens of said democratic state. Perhaps your influence will be much wider and your authority and moral suasion that you seemingly speak with will be more credible.
While there is and should be no doubt that things could have been done a bit better, what has happened in Tivoli Gardens need not have happened if the governments, over the years, had been doing their job in terms of trying to help the less fortunate in Jamaican society. We cannot call ourselves a just, humane, Christian and democratic society and yet we tolerate and even promote the gross inequality in our society.
We can't consider ourselves a Christian society yet violate the tenet that how we treat the less fortunate in society is how we treat God himself. We know that criminality and corruption is rife, not only in government but also within the wider Jamaican society and that they must be seriously and thoughtfully addressed.
We know that the leaderships of the two major political parties in Jamaica are not paragons of virtue and it is incumbent upon folks to not only ask but demand better from those who lead and aspire to lead. This is an opportunity for a different and better type of leadership to make its presence felt and demonstrated in Jamaica. We need our leaders to rise to the occasion and just do it.
Jamaica's 9-11 Moment
Revive the NDM Anyone?
Mr. Dawes – you seem to accept everything from the security forces as gospel. On the matter of phones being confiscated, this was something just thrown out there without any evidence whatsoever.
And ironically while they made this claim they were at the same time advising them where to call to give information – go figure.
I was personally in touch with people during the ordeal via said cell phone – so I know the claim is rubbish.
It would seem that there is something in our psyche that if we do not have a bloodbath somehow we are not happy.
How has the country benefited from the massacre brought on by the security forces' grand adventure?
Do you feel safer now that "dem shot up sum a dem people from dung a Tivoli"?
The sooner we lean towards intelligent problem solving methods and step back from the "Saul has killed his thousands, but David has killed his tens of thousands" approach the better we will be.
Regarding the criticism of human rights organisations , that they should focus on violations by criminals/terrorists.
The state and its agencies are identifiable the criminals are not.
The state is bound by laws, the criminals are not
If the state wants to be the equal of criminals in lawlessness, then thats a recipe for disaster
Trevor Dawes
That the J'can security forces, particularly the JCF, have a sorry reputation for abuses and extra-judicial killings I am not questioning. That they, or rogue elements within the security forces, in all likelihood, engaged in abuses and extra-judicial killings in TG I'm not questioning. However, to belittle the point that folks in TG who might have considered leaving before what went down happened and were prevented from doing so by goons within TG is disingenuous. I don't care if these goons are nameless. When folks are given fair warning of an impending disaster and are then forcibly prevented (on the order of death?) from taking measures to protect themselves that is a human rights violation. Folks like Amnesty Int'l and Americas Watch have criticized both the Colombian gov't and the FARC for human rights violations and the last time I checked, the FARC was not a gov't entity. In fact, the FARC is listed as a terrorist organization by both the US and the EU. Amnesty Int'l has also criticized non-government terrorist groups in the Middle East as well as the Israeli gov't for human rights abuses.
Mr. Hunter, everyone now knows that Mr. Coke's outfit is the Shower Posse so to plead ignorance in this instance is a rather specious argument to make. That they and their sympathizers would forcibly prevent decent folks in TG from leaving or having any means of contact with loved ones from outside TG is a human rights violation. When one's right to freely speak/express an opinion and to move about freely and safely are forcibly curbed/curtailed without a legitimate reason by any party in any country that is a human rights violation. That Ja. has had lousy governments and governance over these many years goes without saying but to imply that it's only the state that has infringed upon and/or otherwise violated people's human rights is a bogus argument to make. I fail to see where it's asking too much of folks like the JFJ to excoriate these folks for putting good folks in harm's way by their deliberately irresponsible actions.
I'll feel safer in Ja. when you have a better gov't that will more ably and effectively address the issues that bedevil it. The same way I have never bought into the notion that if Reneto Adams was still in the JCF crime would be less is the same way what happened in TG won't really solve anything if a comprehensive anti-crime strategy and social intervention are not put in place to address crime and its (prospective) perpetrators. When combined with enforcement and implementation of strong anti-corruption measures in/by gov't and the wider society then and only then will I start to feel some sense of safety.
Mr. Dawes – There is no evidence that people were prevented from having any contact by phone with their loved ones outside of TG.
I spoke to persons during the ordeal. The media spoke to persons during the ordeal. The claim is provably false.
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What is the GATT (General Agreement on Tariffs and Trade)?
Why was the GATT Created?
How Does the GATT Work?
What Are the Principles of GATT?
Member Countries of GATT
Pros and Cons of the GATT
What is the Relationship Between GATT and WTO?
Home » Blog » Investments » General Agreement on Tariffs and Trade (GATT)
General Agreement on Tariffs and Trade (GATT) – Its Role in International Trade
Post World War 2, the economies were drained and needed significant restructuring. Hence, several nations came together to support each other. This is when GATT or General Agreement on Tariffs and Trade came into the picture. GATT was formed when 23 countries joined hands and signed a legal agreement to minimise trade barriers among countries by reducing tariffs, quotas, and subsidies.
Read this blog to learn about GATT, its importance in foreign trade and its principles.
The full form of GATT is the General Agreement on Tariffs and Trade. History beckons that the agreement was signed on 30th October 1947. Twenty-three countries came together post World War 2 to sign the agreement.
The primary objective of the GATT agreement was to reduce trade restrictions by revising or removing certain tariffs, subsidies, and quotas. This was done at a time when international trade was affected by the ills of war.
The GATT aimed to improve existing international relations by making trade easier. It consisted of a set of rules that defined the new trade restrictions that were much more relaxed as compared to the ones that existed before. The agreement also established a system to resolve trade-related disputes among nations.
It is important to note that the World Trade Organization was established because of GATT; which is why, GATT and WTO go hand in hand. The World Trade Organization was established on 1st January 1995, and the body was responsible for extending the application of GATT.
The GATT agreement aimed at resolving a wide variety of issues. However, most of these issues were related to trade and barriers to trade. Some of the major reasons why GATT came into existence are:
The primary motive of GATT was to establish a system to regulate the policies of the pre-war protectionist period. The agreement aimed at restricting or removing quantitative trade barriers like trade controls between two countries.
The other important motive of the GATT agreement is to provide a system to resolve commercial conflicts among nations. Therefore, a framework to resolve these conflicts and conduct multilateral tariff reduction negotiations was added to the agreement.
GATT established a set of trading standards, and hence, it served the purpose of aligning the trade practices of different countries
The GATT agreement was a successful intervention as several trade reforms were brought about post its implementation.
The primary purpose of GATT was to eliminate different kinds of trade protectionism imposed by nations worldwide. The GATT also contributed to reviving economies dealing with the after-effects of World war 2.
Three Provisions of GATT
GATT works on three main provisions.
As per the first provision, all the member nations must give each other the status of the most favoured nation. As per the status, the tariffs and other quantitative restrictions would be the same for all nations. However, the special tariffs imposed on the British Commonwealth countries and customs unions were not under the purview of GATT.
The second provision included the number of imports on which there will be no trade restrictions. However, there were some exclusions to this provision:
In case of a surplus of agricultural produce
If the country was facing issues with its balance of payments due to a reduction in the foreign exchange reserves
Counties that were emerging and needed to protect their industries
Issues involving national security
The third provision was added to the GATT agreement in 1965. According to the provision, the developed countries must agree to remove import tariffs from developing countries. The primary motive of this provision was to support developing countries. Based on these three provisions, the GATT works.
A set of principles governs the GATT. These principles are discussed in detail below.
The most crucial principle of GATT is trade without discrimination. The principal of the most favoured nation was made a part of GATT, as non-discrimination was a primary principle of the agreement. As per the principle, no country should try to take advantage of another country's economic condition.
The second principle ensures that tariffs protect the domestic industries. Hence, GATT promoted customs tariffs over any other form of trade restrictions.
The promotion of fair competition is another important principle. Several countries practised dumping goods, and the principle addressed the issue.
The prohibition of quantitative trade restrictions is the driving principle of GATT. The only exception to this principle could be exercised if the country faced issues related to the balance of payments.
The principle of possible emergency actions is another vital aspect of GATT. According to this principle, a country can ask for release from a particular GATT obligation. The country will have to follow the waiver procedures stated in the agreement. This principle can be exercised only if the economic or trade circumstances of the country are bad.
Another principle that is a part of GATT is regional trading agreements. Under this policy, an exception to most favoured nations can be exercised. These exceptions will be granted as a customs union or a free trade area.
Settling trade disputes is another principle of GATT. As per the agreement, GATT performs regular activities like consultation, dispute settlement, etc.
All the principles stated above are important aspects of GATT. All decisions made under GATT are based on these principles.
The GATT had 23 members when it was established. These countries included Australia, Belgium, Brazil, Burma, Canada, Czechoslovakia, Ceylon (now Sri Lanka), Chile, China, Netherlands, Cuba, France, India, Lebanon, Luxembourg, Norway, New Zealand, Pakistan, Syria, Southern Rhodesia, South Africa, the United Kingdom, and the United States.
The number of members increased from 23 to 128 in 1994 and more countries came under the purview of GATT. Hence, the trade patterns could be standardised at a larger level.
The implementation of GATT was a milestone in World History. However, GATT has its own set of pros and cons. Let's understand both aspects:
1. Pros
Improves International Trade Relations
GATT eliminated several trade barriers and reduced tariffs. Hence, the countries became more open to trading with each other. Also, they realised the advantages of participating in free trade, and the number of signatories to GATT increased from 23 to 128.
Promotion of Harmony and Peace
Post World War 2, several countries came together for the first time to take a collective decision. Hence, the agreement promoted world peace and collaboration. Also, the European countries were struggling, and a war-like situation was built. However, GATT kept the situation in check and helped reduce the possibility of war.
Better Communication among Nations
GATT incentivised nations to interact with each other and improve their trade relations. Hence, the nations tried to understand the problems in other nations and used effective communication to solve these problems.
2. Cons
Impact on Domestic Industries
With the implementation of GATT, more countries started importing goods instead of promoting their domestic industries. Therefore, the unemployment rates of different countries shot up. GATT enabled rich countries to increase production and push the products to other nations. Hence, the middle and low-income nations suffered a lot.
Exposure to Risk
The trade of services was not under the purview of GATT. Hence, services like finance, technology, etc. expanded worldwide, and only a few nations dominated these industries. Hence, an impact on any of these nations impacted the entire economy.
The Reduced role of the Government
Once a country signs an agreement like GATT, it must abide by all its principles. Hence, the government loses control over its own country and its people.
GATT and WTO are related to each other as GATT became a part of WTO post its incorporation. GATT did not cover several aspects of world trade. Therefore, there was a need for a stronger body to take care of the entire aspect of world trade. This led to the establishment of the World Trade Organization.
WTO is a permanent body and GATT came under its umbrella. The WTO took over GATT and came up with overarching principles that covered services and intellectual property apart from goods.
The GATT shaped world trade as it was the first agreement that came into existence to reduce trade barriers. The 23 countries that signed the GATT agreement wanted to promote free trade of goods among nations. The GATT also lived up to its expectations as it conducted several negotiations to improve world trade.
However, due to a lack of coherent structure, it was replaced by the World Trade Organisation. The World Trade Organization has developed several policies that enforce different aspects of GATT. Hence, the GATT still functions under the umbrella of WTO.
Q1. When was the GATT agreement signed for the first time?
Ans. The GATT agreement was signed on 30th October 1947, and 23 countries came together to sign the agreement.
Q2. What is the history of GATT?
Ans: GATT was established following World War II as a way to help rebuild the global economy and promote international trade. It was originally signed by 23 countries and has since grown to include more than 120 member countries. GATT was replaced by the World Trade Organization (WTO) in 1995.
Q3. Which is the driving principle of GATT?
Ans. The driving principle of GATT is the Most Favoured Nation principle. However, other principles, like the prohibition of quantitative trade restrictions, are important.
Q4. When was the WTO formed?
Ans. The World Trade Organization (WTO) was formed on January 1, 1995. It was established as a successor to the General Agreement on Tariffs and Trade (GATT), which had been in operation since 1947. The WTO is a global organisation that deals with the rules of trade between nations and is headquartered in Geneva, Switzerland. It provides a forum for governments to negotiate trade agreements and settles trade disputes between member countries.
Q5. How does GATT promote free trade?
Ans: GATT promotes free trade by establishing rules and procedures for the settlement of trade disputes and by encouraging countries to lower their trade barriers and reduce their tariffs on imported goods. This helps to create a level playing field for all participating countries and enables them to trade with each other more freely.
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This article has been prepared on the basis of internal data, publicly available information and other sources believed to be reliable. The information contained in this article is for general purposes only and not a complete disclosure of every material fact. It should not be construed as investment advice to any party. The article does not warrant the completeness or accuracy of the information, and disclaims all liabilities, losses and damages arising out of the use of this information. Readers shall be fully liable/responsible for any decision taken on the basis of this article.
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redpajama_set_name: RedPajamaCommonCrawl


Are we headed for another Great Depression???
History has a way of repeating itself, however is now one of those times? After all, this past week was the WORST week in the 112 year history of the US stock market (yes, worse than the week of Black Thursday that some say began the Great Depression). So is the worst over, or still yet to come with a possible drop on the Dow to 4,000?
As business-owners and Americans in general, what do we do with our money at this point?
Stock market crash – as mentioned above we've had the worst stock market crash in history so this is undeniable.
Global Affect – dozens of countries were affected by the Great Depression not just the US and now, just as back then, what bodes ill for the US will have wide-reaching repercussions. Did you read about the $400 billion German Bailout for instance?
Huge Personal Debt – One of the primary causes for the GD was the cheap availability of money for businesses and individuals to borrow. When people couldn't make the payments on those notes, things got ugly (to the tune of 9,000 banks closing from 1930-1933). Banks then called for people who were making payments to immediately pay off the principal in full… Those people obviously couldn't pay off the principal in full, so the cycle of economic collapse cascaded… Don't get me wrong, I understand that the average household is not carrying $8,000 but instead is carrying much less and most people are paying those cards off every month (about 55%). However, with the sub-prime mortgage fiasco, there are plenty of people with mortgages they can't afford (and couldn't afford when they took them out).
Presidential candidates with no understanding of economics – If we look at Obama and McCain's policies in detail we'll see how they're making the same mistakes now as Herbert Hoover and then FDR did back then.
No Gold Standard – We no longer base our money and printing it on the amount of gold in the US Treasury. The requirement to base our money on Gold theoretically contributed to severe deflation that resulted in the people who managed to get some money from the banks instantly having less value then when they put the money into the bank. Studies have suggested that there was a direct relation between the quickness with which a country abandoned the gold standard and the quickness with which they recovered from the GD. Others suggest that there was no direct correlation. Believe what you will because it's a bit more complicated than just saying the Gold Standard cause the GD which is why point 5 below is so important.
No Longer an Agrarian Society – Even though, with the advent of the automobile in the 10's and 20's, we began our transition to an industrial society, we were still primarily a society that relied on agriculture in the late 1920's. Not until the production required for World War II did we fully transition to an industrialized country. The huge drought that brought on the Dust Bowl was a significant contributor to the length and severity of the GD. Our current knowledge-based society really has fewer "natural disasters" that can exacerbate the stock market drop by actually devaluing the businesses and products they produce.
Unions have artificially driven up wages – in the 1920's and 1930's unions were necessary to help increase wages to a reasonable level so that the workers could afford to purchase the products being produced. Now we have unions that have made it so expensive to produce things businesses can't charge enough money for those products to make a profit and keep those same people employed. The auto industry is the best example of people in the 20's not being able to afford the product they produced while the cost per hour of auto production in the US today is 30 times higher than that of China. Sorry guys, that's just not sustainable or competitive.
No widespread panic – Sure people are pulling out of the stock market, but how many of your friends have started withdrawing their savings from the bank and stuffing their cash under their mattresses? We still fundamentally believe that cash in the bank is safe even if we are doubting that money in the stock market is.
Ben Bernake is the Fed Chairman – Ok, this has less to do with one person, and more to do with the fact that we've had a GD to learn from and study for the last 70 years. With that knowledge we are better prepared to avoid it. Let's face it, Mr. Bernake is the most powerful person in America and has studied the GD at length. Because of this I would argue he better understands the causes and effects than anyone did in the 20's and 30's. Even if he isn't 100% correct on the causes of the GD, he still has a larger pool of knowledge to pull from then anyone did 80 years ago.
We have 4 similarities and 5 differences… So are we headed for another Great Depression???
First off we, as individuals and households, can only directly effect a few of the items above.
We can affect how much personal debt we take on by learning some easy math to understand what our family can afford instead of blanketly trusting a mortgage broker who is paid on commission. Common sense appears to be as lacking back then as it is now.
We can vote for the candidate who has a better chance of improving our economy based on sound economic policies – NOT because they're a war hero or a charismatic speaker. Did I mention a lack of common sense back then and now?
One reason engineers hate economics as much as they hate poetry is because it's all based on theories and opinions. There are no real "economic laws" like our much beloved Newton's Laws of Motion. With that being said neither I or anyone else can predict exactly what can happen… However, every day that we get up believing we still have a job, or that we invest money in the stock market, or that we evaluate a new business for buying, building, and selling we're attempting to predict the future, so why stop now?
That being said, over the next 12 months I plan to buy a lot of stocks! In our buy, build, and sell mentality for growing small businesses there is rarely a case where we can get better returns in the stock market (over which we have no effect) then we do with our own business. However, if we're at the worst point in the history of the stock market, yet 1-in-10 companies have more cash stock-piled then there current market capitalization, then this is the ripest stock market for investing in history!
Let me rephrase that, nearly 10% (876 of 9,194) of the stock's tracked by Standard and Poor's compustat research service have more cash in the bank than the entire company is worth based on simply multiplying the stock price by the number of outstanding shares. If you ever encounter an opportunity to buy a business for $100,000 that includes $120,000 in cash in the bank and you don't have $100,000 please let me know immediately! In essence, 10% of our stock market is in that position. As a rock-climber in West Virginia once taught me at those points of extreme jubilation, Wahootey-Hootey!
Does that mean we've hit bottom? Who knows? More importantly, who cares? Invest little by little over the next 12-months as the stock market continues to move and you may have the greatest investing opportunity of your life. The same could have been said for the Great Depression… Then again, I'm just a mechanical engineer who owns a few small businesses – what do I know?
P.S. In the next blog we'll look at the failed economic policies that caused the Great Depression to be as long and severe as it was and which ones the candidates are still foolishly trying.
Once again Brian you are squeezing Lemons and adding the sugar.
Great additions can be had during these troubled times.


I see it in the administration pannel but only here, anyone can help me please?
Grab the latest release at .com and install it.
First disable your copy, delete data and delete your old files from your server.
Then copy the latest release over to your server and enable it. Check settings in acp.
I have installed Mchat in a few 3.2.1 boards and it shows.
Make sure permissions in acp are set to show Mchat.


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Plagues on Houses
European Royals Feel the Effects of the Coronavirus
by Kyle Munzenrieder
For a Spanish royal, looking ravishing in red is a must. The former news anchor proved she had what it took early on, with this red gown at the wedding of Prince Frederik of Denmark in 2004.
What was true during the days of the bubonic plague remains true during the days of the coronavirus: royal blood offers no special protections against a pandemic. In fact, the various royal houses across Europe are already feeling the effects of the COVID-19 outbreak. The archduke of Austria Karl von Habsburg has already tested positive for the virus, while King Felipe VI and Queen Letizia of Spain are awaiting test results after coming into contact with another person infected with the disease.
Despite his positive results, Karl of Austria, the 59-year-old head of the House of Habsburg-Lorraine, remains in good spirits.
"It's annoying, but I'm fine. It's not the black plague," he told the Austrian newspaper Kleine Zeitung. "I thought it was the usual flu. When a friend called me that he had a positive test at a congress in Switzerland, I was also tested."
Habsburg is now in quarantine in his home in Lower Austria, and avoiding direct contact with his other family members, including his occasional fashion model daughter Eleonore and his professional race car driver son Ferdinand. It should be noted that the Habsburgs are royalty in a hereditary sense only, as Austria no longer legally recognizes the country's former monarchy or nobility. Still, the family remains prominent in Austrian society.
Spain, however, still recognizes its monarchy and entrusts them to carry out royal duties. That's how King Felipe and Queen Letizia may have come into contact with the virus. The pair had met with the Minister of Equality, Irene Montero, on Friday. The Minister has since tested positive for COVID-19 (her domestic partner, Pablo Iglesias Turrión, Spain's Second Deputy Prime Minister, is now also under quarantine).
The French President Emmanuel Macron and his wife, Brigitte Macron, welcome King Felipe and Queen Letizia of Spain prior to a lunch at the Élysée Presidential Palace on March 11, 2020, in Paris. Photographed by Chesnot/Getty Images
The royal house plans to publicly announce the results of the test when they're available, but a positive test could have far-reaching consequences. The king and queen met with the French President Emmanuel Macron and his wife, Brigitte, just yesterday. Even if one cares little for health updates on the royal families of Europe, such high-profile cases do illustrate the chain of caution that even one positive test can set off.
The couples did take precautions during the meeting, though. Instead of shaking hands, they offered each other namastes (a slight bow with pressed hands).
Other royal families are feeling the effects as well.
Monaco's royals have postponed their annual (and extravagant) Rose Ball for the first time in its history. The event, first started by Princess Grace of Monaco, draws a fashion- and society-heavy crowd from across the globe. For several years, the late Karl Lagerfeld designed the event. The Norwegian royal family has canceled all events through Easter. The Danish royal family returned home after cutting short a trip to Switzerland.
The British royal family, however, stands out from the crowd. While Prince Charles has been spotted offering namastes of his own, 93-year-old Queen Elizabeth II caused concern when she offered a gloveless handshake while awarding a professor with a Royal order. According to Vanity Fair, the House of Windsor seems to be operating under a "business as usual" policy at the moment, with multiple public appearances and even some international travel on their various agendas.
It's possible that may change in the near future. The BBC reported that today marked the highest number of new cases detected in the U.K. so far. The country's total now stands at 460 detected cases, with 10 deaths. As is true in all countries in which the coronavirus has been detected, those numbers are only expected to rise over the coming weeks.
While America does not have a royal family, the coronavirus diagnosis of Tom Hanks and his wife, Rita Wilson, was still received like a ceremonial symbol that the nation had become infected.
Related: How Is Hollywood Handling Coronavirus?
coronavirus king felipe King Felipe VI of Spain queen elizabeth queen elizabeth ii queen letizia Queen Letizia of Spain rose ball


singosarijothanks for the deal! fast response!
Bought FROM China during holidays. No brand. Material is thick Comes with embodiery. Smart for office wear FOR S size people. Non stretchable.
Helping a friend. Still new doesn't fit on her so selling away.
Only worn thrice !! Super cute parka that can go with any outfit you're wearing keke :) Price can nego a bit !!
Used once only when I went to Taiwan. Size 16. Slightly big. But good when you are layering clothes.
Condition: New (haven't worn before) 10/10 💯 ⚠ Tag as Size S PTP: 118cm Length: 75cm Sleeve: 43cm Shoulder: 62cm Selling off real cheapppppz!
Used Once Size EUR36 Army Green RTP was S$69 Super comfortable material! Like lyocell.
Good for cold climates! Can fit S or M size. Strap tie included. Long enough to cover till knee area to stay warm!


text:
Q: xpages getDocument().getUniversalID() I just want to test something about getting the UniversalID:
I create a computed field:
 <xp:text escape="true" id="computedField3"
    value="#{javascript:Cdoc.getDocument().getUniversalID()}">
</xp:text>

When I compose the doc. content which is on a Xpage, the computed field is already having some UNID and it is changing if I hit refresh. In lotus notes programming, the UNID could be get only if the current document was saved, having the default value @Text(@DocumentUniqueId).
Should I save first the Cdoc datasource to get the correct UNID? I know I'm missing something.
Thanks for your time

A: If you refresh your page in browser then actually a new document gets created. That's why you get a different UNID.
From your previous questions I know that you define your Cdoc as a data source with
<xp:this.data>
    <xp:dominoDocument
        var="Cdoc"
        formName="fmPersContact">
    </xp:dominoDocument>
</xp:this.data>

and that means that this Cdoc is created every time you open this XPage.
Update:
In addition, you get also a different UNID every time your field gets calculated on server  when you do a partial refresh and document is not saved yet.

redpajama_set_name: RedPajamaStackExchange


Magnificent house for sale in Pyla, Larnaca. This amazing property is an astonishing example of real estates in Cyprus. Featuring 3 bedrooms, master with en suite , open plan kitchen and dining room, garden and a private parking. Amenities like school, bank, shop, etc very close by. Truly a magnificent house!


I must say, I don't quite understand the reason behind this new forum of yours. I guess I could understand you wanting to spread your wings and promote yourself as the master spriter you are with your own website, but why make a whole new forum? Why not just come back to Vortex? That place has gone nowhere but downhill since you left. Not saying it's your fault, but your presence would make that place flourish again, without a doubt.
It just seems kind of treacherous that you made a whole new forum, in spite of all your old friends at the DBZ Vortex.


text:
module.exports = {
	user: null
};

redpajama_set_name: RedPajamaGithub


text:
Renowned South African author, Karel Schoeman commits suicide
Renowned South African author Karel Schoeman has committed suicide, his lawyer Carl van Rensburg confirmed Wednesday.
Media reports said Schoeman died in a retirement home in the city of Bloemfontein at the age of 77.
Schoeman was one of South Africa's most prolific and prize-winning authors and he was even tipped for the Nobel Prize.
His relatively unknown status has been attributed to his writing primarily in Afrikaans, South Africa's Dutch-related language.
Van Rensburg denied reports that he had stopped taking food and water.
"He found another way to end his life.
"I presume some sort of medication must have been involved," he said.
Van Rensburg said Schoeman had left a letter behind.
The daily Times Live quoted the letter as saying he did not want to be old and become a burden to anyone.
Schoeman was a South African novelist, historian, translator and man of letters.
He was the author of 19 novels and numerous works of history.
Schoeman wrote primarily in Afrikaans, although several of his non-fiction books were originally written in English.
His novels are increasingly being translated into other languages, notably, English, French and Dutch.
Schoeman won the most prestigious Afrikaans literary award, the Hertzog Prize, three times: in 1971 (for By Fakkellig, 'n Lug vol helder wolke and Spiraal), 1986 ('n Ander land) and in 1995 (Hierdie lewe).
The Recht Malan Prize for "excellence in the field of non-fiction books" was awarded to him four times.
On the retirement of President Nelson Mandela in 1999, Schoeman was one of only two writers to be awarded the State President Award: Order for Excellent Service.
In more recent years, his fiction garnered much praise in France, winning inter alia the prestigious Prix du Meilleur Livre Étranger in 2009.
His 1972 novel, Na die Geliefde Land (literally: To the Beloved Country), was made into an award-winning feature film, Promised Land in 2002, with a screenplay by Jason Xenopoulos.
Schoeman has produced and published several screenplays, including an adaptation of his first novel, Veldslag, some of which were broadcast on South African national television during the 1980s. (NAN)
Britain won't pay 100bn Euros for Brexit, minister says
5 Nigerian movies listed for 2017 Nollywood Week Paris awards
N' Korea confirms arrest of US citizen over alleged action to topple govt


text:
Q: Visual Studio 2010 code display colour scheme - where do I find some properties? I'm working on my own colour scheme for displaying code in visual studio. I can't find some text section name so I don't know where to change its colour. :( Can anybody help me and tell me where do  I find them, I mean what is the name of the following sections:

*

*The grey one (documentation tag value and it's quote) - picture below

(source: yfrog.com)

*The olive colour: header of a asp.net in vb language document. - <% and underline.

http://img12.yfrog.com/img12/7375/headerqt.png (NOTE: image is now broken)
To write my code I use vb.net language.

A: XML Doc comment, XML Doc Quote should be what your looking for. VB user types, User types and keyword also.
You might want to save yourself some time, i just did my color scheme, which i call Steam (based on Steam Platform from valve). It kind of looks like what your going for
I can't post a screenshot since i am new, but here is a download link. You can import it via the tools menu in VS. It includes resharper color settings.
Steam for VS 2010/08

A: The first one is XML Doc Attribute.
The second one is HTML Element Name.


text:
Justice for Kim Montelaro>
Once again, Christopher Righetti is being considered for early release, despite receiving a Life sentence for the abduction, rape & murder of 20-year-old Kim Montelaro. We've been told that his hearing will be held sometime in June 2021. Keep NJ Safe is calling upon members of the community to write to the NJ State Parole Board and urge them to deny Righetti's parole. Letters must be received by May 5, 2021.
Please join us in showing support for the Montelaro Family by submitting a letter to the Parole Board. We also ask that you take a moment to sign our online petition, at this link: SIGN THE PETITION TO DENY PAROLE FOR CHRISTOPHER RIGHETTI
Here is a sample letter; please feel free to add your own personal thoughts to customize your correspondence. Due to the tight timeline, we are also accepting letters via email at info(at)keepnjsafe.org
TO: NJ State Parole Board, P.O. Box 862, Trenton NJ 08625 ATTN: Tanya Milton, Victim Services Coordinator
RE: Christopher Righetti, Prisoner #59431, SBI# 000149274C
On August 31, 1976, 20-year-old New Milford resident Kim Montelaro was forcibly abducted, raped and brutally murdered by repeat offender, Christopher Righetti, Prisoner # 59431. His crime was so depraved and violent, he was given a Life sentence. Despite the court's determination that Righetti should remain incarcerated for the remainder of his life, he is now being considered for parole.
To this day, Righetti has never shown any remorse for his crime, and he remains a danger to the community. According to evidence detailed in the coroner's report, Kim's sexual assault was brutal, and she died an agonizing death: stabbed repeatedly in the neck and chest and left in a ditch, drowning in her own blood.
Righetti is a serial rapist: he committed his first rape–assaulting a 21-year-old woman at knifepoint–when he was just 14 years old, and shortly after being released from juvenile detention for that crime, he attempted to assault another young woman, before raping and murdering Kim Montelaro. Recent studies of sex offenders, in particular "stranger rapists" who do not know their victims, show that biggest predictor of recidivism is when rapist has a history of multiple sexual assaults against multiple victims. Righetti is a violent sex offender who is likely to rape and kill again, and must not be released back into society.
I urge the New Jersey Parole Board to deny Christopher Righetti's request for parole, and force him to serve out the full remainder of his Life sentence.
(YOUR NAME & ADDRESS HERE)
UPDATE: The Record did a great job covering our fight. You can read the article at NorthJersey.com: https://www.northjersey.com/story/news/bergen/paramus/2021/04/20/kim-montelaro-killing-1976-family-opposes-chris-righetti-parole-hearing/7220417002/
UPDATE #2: Help Us Rally Elected Officials to Support of Our Efforts! Please contact your local, county, and elected officials and urge them to lend their support to our efforts, by signing our petition, writing a letter as instructed above, or passing an official Resolution. CLICK HERE TO SEE A SAMPLE LETTER YOU CAN CUSTOMIZE, ALONG WITH A SAMPLE RESOLUTION
Tags: christopher righetti, justice, kim montelaro, murder, parole, rape
Previous PostCALL TO ACTION: Please Sign Our Petition to Deny Parole for Angelo Speziale
Next PostUPDATE: Righetti Future Parole Date Set at 120 months
Sample Letter to NJ Parole Board
UPDATE: Righetti Future Parole Date Set at 120 months
Resolution to Oppose Parole for Righetti


You're making me wish I still lived in New Hampshire! It sounds like quite a nice little coffee spot.
So, did you go back and try some other roasts? What is your favorite?
Previous Previous post: Where's my cardboard laptop?


text:
La sélégiline est une molécule de la classe des amphétamines, plus précisément dérivée de la méthamphétamine. C'est un inhibiteur irréversible de la monoamine oxydase B (IMAO-B), permettant l'inhibition de la dégradation des catécholamines (adrénaline, noradrénaline et dopamine) et de la sérotonine.

Elle agit chez l'humain comme un inhibiteur de la monoamine oxydase B (IMAO-B) et est utilisée pour traiter la maladie de Parkinson. En médecine vétérinaire elle est utilisée dans le traitement des troubles comportementaux tels que l'hypersensibilité, l'hyperactivité, l'anxiété de séparation et les phobies, en association avec des thérapies comportementales.

Dépression
La sélégiline est aussi utilisée dans certains pays en timbre transdermique dans le traitement de la dépression sous la marque Emsam.

Spécialités contenant de la sélégiline

 Médicaments contenant de la sélégiline commercialisés en France :
 Déprényl

Références

Alcyne
Amphétamine
Nootropique
Antiparkinsonien
Inhibiteur de monoamine oxydase
Médicament énantiopur

redpajama_set_name: RedPajamaWikipedia


Wondering which Corporate Removals service would be best for your property based in Flat 13, Beaumaris Tower, London, W3?
Place your trust in our Corporate Removals company that operates in North Acton Ealing London W3 and we guarantee a seamless removal. Our company is known for providing exceptional Corporate Removals services at pocket friendly prices.
If the number or weight of your items differs from the one you have initially discussed with our professional North Acton Ealing London W3 team over the phone or via email, we may ask you to pay additional charges after our Corporate Removals team visits your address in North Acton Ealing London W3 accommodate your moving request.


She's been jetting around the world promoting her acclaimed new movie.
And Claire Foy was all smiles as she attended a special BAFTA screening of First Man in New York on Tuesday night.
The 34-year-old actress beamed as she sat with the film's director Damien Chazelle for a question and answer session.
The Crown star looked gorgeous in an elegant navy jumper with a daringly low-cut neckline and a stunning midi-skirt.
She complemented the ensemble with a pair of matching black peep-toe heels and a sophisticated gold chain.
Claire's cropped brunette locks were swept to one side while she wore a slick of eyeliner and lipstick to accentuate her pretty features.
The actor's new film is based on a true story and follows the life of Neil Armstrong on his quest to become the first man to walk on the moon.


At the start of 2018, public pension plans and insurance companies accounted for about 91% of institutional assets focused on environmental, social and governance factor investing, with educational institutions a distant third at 6% of total ESG assets. The U.S. SIF Foundation surveyed 496 institutional investors managing an aggregate $5.6 trillion in ESG-focused assets.
Screens focused on removing exposure to specific consumer products rose the most in 2018 compared to data collected in 2016. Those screens involved $2.9 trillion in managed assets, up from $1.5 trillion, a 90% increase. Socially screened assets increased about 20%, but still represent the largest factor screen. Assets may fall into multiple factor screen categories, so overlap is expected. Socially based factors have historically been the most common ESG screen, and 2018 data represent about 94% of the total institutional assets surveyed.
Among the top specific issues, almost $3 trillion was screened for conflict risks, or companies that support terrorism or repressive regimes, directly or indirectly. Filtering out tobacco companies increased 121% since 2016 to $2.56 trillion, while issues surrounding corporate governance increased 40% on average.


Whee! All The Way Home: Wordy Wednesday #84: Boo-Yah!
Memo to future self: Do not ask household members Sunday morning at 8 o'clock, "Who wants to come to church with me?" Instead, say, "I'm leaving for church at 8:50. Be ready by then."
I'm happy, though, that my errand buddy, as expected, happily accompanies me. A recovering Catholic by trade, I have managed to convert only Youngest to the joys of the rituals. He enjoys the same hymns and such as I do. He is as resistant to some of the trappings -- like the seeming-to-never-end giving of peace -- as I am.
May God look after all his soldiers. We remember those who have served and continue to serve so that we might be safe, particularly Pete's many uncles who served in World War II and my own Dad, an Air Force career man.
Halle-boo-yah is THE. AWESOME. I think the Lord is well pleased.


text:
Q: what's the difference between xgb.callback.TrainingCallback and xgb.callback.EarlyStopping when use these api to early stopping? xgb.callback.TrainingCallback can also stop training by overwrite after_iteration function
 def after_iteration(self, model, epoch, evals_log):

And how these API influence the final best_iteration (compare with xbg.train(early_stopping_rounds=xx))


text:
[RFC PATCH 0/5] XAudio PE conversion.
Zebediah Figura (she/her) zfigura at codeweavers.com
Previous message (by thread): [RFC PATCH 0/5] XAudio PE conversion.
Next message (by thread): [RFC PATCH 0/5] XAudio PE conversion.
I know I'm representing the minority opinion here, but I'd like to offer
my objections anyway :-)
I think the solution I originally proposed doesn't make a lot of sense
in retrospect. However, I don't like this one either.
I've tried to rethink my position to be more reasonable, and I'd like
whatever solution we come up with to satisfy three things:
(1) I really don't want to have to build any libraries that aren't part
of Wine. More importantly, I don't want anyone who's not a regular Wine
developer to ever have to build any libraries that aren't part of Wine.
Also, if I do need to build (say) libvkd3d-shader, I want to *only* have
to build libvkd3d-shader and not all of the Wine dependencies at once.
This is quite likely the only thing that holds me back from contributing
to wine-mono (not that this is entirely Esme's fault; the problem
affects mono upstream, although wine-mono has doubled down on it)
(2) I would like bisecting dependencies to not be a pain. As someone who
will be working on vkd3d a lot, this is quite important to me. Ideally
this means that the dependencies should exist in shared libraries, not
static ones.
I would also like to be able to develop in a separate tree, since git
submodules are terrible for doing active development on a component.
Rémi's proposed solution does not really allow for that as far as I can
tell.
As an aside, I still think there is something to be gained in using
shared libraries to reduce disk space. Almost all of our PE dependencies
are not only shared across multiple DLLs, but will often be loaded
multiple times in the same process (vkd3d, faudio, gnutls, libpng, zlib,
freetype, mpg123 all come immediately to mind. To some degree we can try
to abstract that out with our own shared-to-static shims, but that takes
some work which I think is rather unnecessary.)
(3) Most importantly, I would like to coöperate with distributions. As I
understand, they already don't like the way we distribute wine-mono and
wine-gecko, and I don't think we should annoy them any further by going
behind their back and distributing more pre-built libraries.
I know people here think that they won't want to distribute PE
libraries, but I'm inclined to think that at least some distributions
won't be happy with our proposed solution either. See [1] [2] [3] [4]
for popular distributions trying to discourage source imports and static
libraries. I get that we're a special case, and maybe distributions will
think so too, but I really want to again argue that we shouldn't be
making that decision for them.
ἔρρωσθε,
Zebediah
[1] https://wiki.debian.org/EmbeddedCopies
[2] https://fedoraproject.org/wiki/Bundled_Libraries
https://docs.fedoraproject.org/en-US/packaging-guidelines/#packaging-static-libraries
[4] https://wiki.gentoo.org/wiki/Why_not_bundle_dependencies


text:
Q: Calculate with sequences from OEIS Is there any easy way to do calculations with sequences from OEIS online? For example
I would like to input something like:
(A007620(n+1) / 2 )  + A000027(n)

and then get something like
4, 8, 12, 14, 17, 20, ...

I tried Wolfram Alpha which can access the sequences but I did not find any way to calculate with them there.

A: The problem is well discussed here!
One may write functions in Mathematica that work with OEIS data and some of the answers include functionality that one may build upon.

A: If I am writing a program to handle the data, I would just copy the first few hundred terms of the series into a txt document and directly access it as an array.


Bixa orellana L. has been traditionally used in Central and South America to treat a number of ailments, including internal inflammation, and in other tropical countries like Malaysia as treatment for gastric ulcers and stomach discomfort. The current study aimed to determine the major chemical constituents of the aqueous extract of B. orellana (AEBO) and to evaluate the antihistamine activity of AEBO during acute inflammation induced in rats.
Acute inflammation was produced by subplantar injection of 0.1 mL of 0.1% histamine into the right hind paw of each rat in the control and treatment groups. The degree of edema was measured before injection and at the time points of 30, 60, 120, 180, 240 and 300 min after injection. Changes of peritoneal vascular permeability were studied using Evans blue dye as a detector. Vascular permeability was evaluated by the amount of dye leakage into the peritoneal cavity in rats. To evaluate the inhibitory effect of AEBO on biochemical mediators of vascular permeability, the levels of nitric oxide (NO) and vascular endothelial growth factor (VEGF) were determined in histamine-treated paw tissues. The major constituents of AEBO were determined by gas chromatography–mass spectrometry (GC-MS) analysis.
AEBO produced a significant inhibition of histamine-induced paw edema starting at 60 min time point, with maximal percentage of inhibition (60.25%) achieved with a dose of 150 mg/kg of AEBO at 60 min time point. Up to 99% of increased peritoneal vascular permeability produced by histamine was successfully suppressed by AEBO. The expression of biochemical mediators of vascular permeability, NO and VEGF, was also found to be downregulated in the AEBO treated group. Gas chromatography–mass spectrometry (GC-MS) analysis revealed that the major constituent in AEBO was acetic acid.
The experimental findings demonstrated that the anti-inflammatory activity of AEBO was due to its inhibitory effect on vascular permeability, which was suppressed as a result of the reduced expression of biochemical mediators (NO and VEGF) in tissues. Our results contribute towards the validation of the traditional use of Bixa orellana in the treatment of inflammatory disorders.
The Bixaceae family is one of the smallest plant families, consisting only of one genus, Bixa. There are only five species grouped under a single genus, and the most common species is Bixa orellana, an evergreen shrub grown not only because of its beautiful red flowers and ornamental red spiny fruits, but also for its economic value. Bixa orellana, also known as "annatto", is native to tropical America , but widely cultivated and naturalized throughout the tropics, including Malaysia. Bixa orellana is well known for its coloring agent and medicinal value. The seeds are sources of food coloring and a dye called annatto. Besides that, they are also used as treatment for illnesses like gonorrhea and asthma and have been traditionally used as gargle for sore throats. The bark and root can be used to treat fever; the leaves are used as a cure for snakebites, jaundice, diabetes and hypertension, especially in Trinidad and Tobago, while also being used as a postpartum medicine in Malaysia . The leaves of Bixa orellana have been reported to have antimicrobial , antifungal, antileishmanial , anticonvulsant, analgesic  and anti-inflammatory activities .
Inflammation limits the damage to the body cells after invasion by foreign organisms or mechanical injury, but if goes uncontrolled and untreated, it becomes a threat leading to other illnesses such as arthritis, cardiovascular disease, asthma, and cancer. Histamine is one of the most common inflammatory mediators; it causes symptoms of allergic reactions that mostly involve acute inflammation mediated by the H1 histamine receptor . The histamine H1 receptor is mainly expressed in endothelial cells, smooth muscle cells and brain, and contributes to vasodilation, increase of vascular permeability  and pain  at the cellular level, while causing enhanced production of intracellular calcium (Ca2+) and nitric oxide (NO)  at the molecular level.
We have previously reported the ability of the aqueous extract of Bixa orellana (AEBO) in suppressing inflammation induced by carrageenan (data not published) and bradykinin . This study aimed to investigate whether the anti-inflammatory activity of AEBO was caused by the blocking of histamine action, and to determine the involvement of two biochemical mediators, NO and vascular endothelial growth factor (VEGF), in the reduction of inflammation by AEBO.
The following chemicals and reagents were used: histamine, loratadine, Evans Blue (Sigma Chemical Co. Ltd, Selangor, Malaysia), nitrite/nitrate assay kit (Roche, Kuala Lumpur, Malaysia) and Murine VEGF ELISA kit (BioVision, USA).
Bixa orellana leaves were procured from around Universiti Putra Malaysia. Leaves were identified and voucher samples (NL16) were deposited at the Phytomedicine Herbarium, Institute of Bioscience, Universiti Putra Malaysia, Selangor. B. orellana leaves were dried in an oven at 60°C for three consecutive days and ground into fine powder. The aqueous extract was obtained by mixing the powder together with distilled water at ratio 1:20, and kept in a water bath (40°C) for 24 h, followed by filtration . The filtrate was kept at −80°C and lyophilized using a freeze drier, yielding 8.5% (w/w). At the time of use, the lyophilized extract was dissolved in distilled water at the desired concentration.
Experiments were conducted using male Sprague–Dawley rats weighing 200–250 g, purchased from Northern RK Supplier, Malaysia and housed at the Animal House of the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia. The animals were divided into groups of six individuals (n = 6) and kept in plastic cages at room temperature (23 ± 1°C) in a 12-h light:dark cycle, with free access to standard chow diet and water. The animals were acclimatized to the laboratory conditions for at least 1 week before the beginning of each experiment. All experiments complied with the current guidelines for the care and use of laboratory animals and were approved by the Animal Care and Use Committee (ACUC), Faculty of Medicine and Health Sciences, Universiti Putra Malaysia (ACUC NO. UPM/FPSKPADS/F01-00176).
The aqueous extract of B. orellana leaves (AEBO) was analyzed by gas chromatography–mass spectrometry (GC-MS-QP5050A-Shimadzu). A Zebron ZB-FFAP capillary column with length 30.0 m x diameter 0.25 mm and film thickness 0.25 μm was used. The column oven temperature was kept at 50°C for 3 min, then increased up to 250°C at a rate of 20°C/min and held at 250°C for 20 min. The carrier gas (helium) was introduced into the column at a flow rate of 1.0 mL/min. Injector and interface temperatures were set to 250°C each. AEBO (1 μL) was injected manually into the GC-MS in splitless mode. Compounds were identified by comparing their mass spectra with those in the NIST library and by comparing their retention times with those of authentic standards.
The effect of oral administration of AEBO was determined by injection of histamine in the subplantar region of the right hind paw, according to the method described by  and . Briefly, rats (n = 6) were pretreated with AEBO at doses of 50 and 150 mg/kg, for 4 consecutive days, before being injected with 0.1 mL histamine (0.1%). Control animals received a similar volume of vehicle (0.1 mL). Loratadine (10 mg/kg), a histamine H1 antagonist, was used as the reference drug and administered 60 min before histamine injection on the fourth day. Edema was identified by the changes in paw volume, measured using a plethysmometer (Model 7140, Ugo Basile, Italy) before histamine administration and at 60, 120, 180 and 240 min after histamine injection.
To evaluate the changes of intraperitoneal vascular permeability induced by histamine, Evans blue dye was used as an indicator according to the method previously described by Whittle . Rats were injected intravenously with 5 mL/kg of 1% Evans blue solution 60 min after the oral administration of AEBO, vehicle, or loratadine. Rats were killed 30 min after the intraperitoneal injection of histamine. The concentration of Evans blue in the peritoneal fluid was measured via spectrophotometry at 610 nm wavelength.
NO was measured according to the method of Moshage et al. , using a commercially available Nitrite/Nitrate Colorimetric Kit (Roche). For this assay, 0.1 mL of 0.1% histamine was injected intraplantarly on the fourth day and the paw tissue obtained was deproteinized with 35% sulfosalicylic acid. The tissues were homogenized and centrifuged to obtain the supernatant. Nitrate (NO3 -) was converted into nitrite (NO2 -) after reacting with nitrate reductase. Total nitrite was measured using Griess reagent with 1:1 ratio and read at OD 540 nm. The sum of nitrite and nitrates obtained from this procedure represented the NO concentration in paw tissue (μM/g wet weight of tissue).
The concentration of VEGF in rat hind paw was determined using Murine VEGF ELISA Kit (BioVision). Analysis of VEGF was performed using standard ELISA methodology according to the kit's manual. Briefly, paw tissue was excised after 6 h of histamine-induced inflammation. The tissues were homogenized in pre-chilled lysis buffer containing protease inhibitor. The homogenate was centrifuged and VEGF level was determined from the supernatant obtained. All assays were performed in triplicate and results were expressed in ng/mL protein.
All data were reported as mean ± SEM; n represented the number of animals in each group. Statistical comparisons were made by ANOVA followed by Tukey's multiple comparison test. P values < 0.05 were considered significant.
Several organic compounds were detected in AEBO by GC-MS (Figure 1). Six major compounds were identified: 2-butanamine (tR; 7.767 min), acetic acid (tR; 8.292 min), pentanoic acid (valeric acid) (tR; 9.583 min), phenol (tR; 11.600 min), pantolactone (tR; 11.817 min), and benzoic acid (tR; 13.850 min) (Table 1).
Major chemical constituents present in the aqueous extract of Bixa orellana leaves.
Exposure of rat's hind paw to histamine resulted in a marked increase of paw tissue weight and skin thickness. Paw weight significantly declined upon oral administration of AEBO (50 and 150 mg/kg) or loratadine (10 mg/kg) at 60 min time point compared with the non-treated group (Figure 2). Moreover, the changes were also significant for the dose of 150 mg/kg of AEBO compared to the non-treated group, from 180 min onwards. Although the paw volume reached its peak 60 min after histamine injection, the maximal edema inhibition was observed 300 min after the administration of 150 mg/kg of AEBO (76.0%). The percentages of inhibition produced by 150 mg/kg of AEBO at each time point (starting from 60 min) were 60.3%, 51.8%, 67.3%, 75.0% and 76.0%.
Effect of AEBO on histamine-induced paw edema in rats. Data are expressed as mean ± SEM, n = 6. Paw volume was measured every 60 min until 300 min. *P < 0.05, significantly different from negative control (histamine only).
As shown in Figure 3, both doses of AEBO (50 and 150 mg/kg) notably inhibited the histamine-induced increase of dye leakage into the peritoneal cavity, with an inhibitory rate up to 99%. The potency of AEBO was similar to that of loratadine (91.1% inhibition).
Effect of AEBO on histamine-induced peritoneal vascular permeability. Evans blue dye was collected and measured by spectrophotometer. Data are presented as mean ± SEM, n = 6. *P < 0.05, significantly different from NC (negative control).
Production of NO in rat's paw was markedly increased in response to histamine (46.2 ± 1.8 μM), but was significantly suppressed by both doses of AEBO (P < 0.05) (Figure 4). The concentrations of NO were reduced to 29.7 ± 1.2 μM and 19.7 ± 1.4 μM after the administration of 50 and 150 mg/kg of AEBO, respectively. On the other hand, loratadine, the reference drug, also significantly inhibited the NO production induced by histamine. However, the inhibition rate of loratadine was not as high as that obtained with both doses of AEBO (50 and 150 mg/kg). This indicated that AEBO had an inhibitory effect on histamine-induced NO production.
Effect of AEBO on histamine-induced NO production in rat's paw. Paw tissue was homogenized and the supernatant was assayed by the Griess reaction. Data are presented as mean ± SEM, n = 6. *P < 0.05, significantly different from control.
Figure 5 shows that oral administration of AEBO significantly suppressed histamine-induced VEGF production in rat's paw. As observed, the highest dose of AEBO (150 mg/kg) had a greater effect (55.9% inhibition) compared with the reference drug, loratadine (~11.2% inhibition). On the other hand, 50 mg/kg of AEBO only showed 36.6% inhibition compared with the non-treated group.
Influence of AEBO on histamine-induced VEGF production in rat's paw. Data are presented as mean ± SEM, n = 6. *P < 0.05, significantly different from NC (negative control).
The present study demonstrated that the aqueous extract of Bixa orellana leaves had anti-inflammatory activity, as shown by the suppression of vascular fluid extravasations produced by histamine. These antihistamine activities, revealed by decreased paw volumes and almost normalized peritoneal vascular permeability, were suspected to be aided by the suppression of other permeability-regulating substances (NO and VEGF).
In our preliminary study, B.orellana exhibited the ability to suppress the inflammatory activities of a number of mediators, with AEBO having inhibited up to 99% of paw edema induced by carrageenan (data not published). Indeed, when bradykinin was later used to induce acute inflammation in the same rat models, it was confirmed that up to 82% of the increased vascular permeability was successfully alleviated upon administration of AEBO . Histamine is one of the inflammogens that contributes to acute inflammation and increase of vascular permeability . The present study documents for the first time the ability of AEBO to suppress the histamine-induced inflammation in rats. Paw edema assay is a useful tool for investigating agents with potential anti-inflammatory capabilities. The present study showed that exposure of rat's paw to histamine triggered an elevation in fluid extravasations from microvessels in the vicinity, an event that led to tissue swelling. The results showed that AEBO was able to significantly suppress histamine-induced paw edema in rats, and this may probably be due to the inhibition of the H1 receptor or other signaling molecules down its pathway. Histamine H1 receptor expressed in endothelial cells of blood vessels is important for regulating vascular permeability , and increased permeability occurs once it is activated.
Inflammatory processes are also characterized by an increase in microvascular permeability to macromolecules. Leakage of Evans blue dye into the peritoneal cavity indicated the formation of gaps or pores in the wall of the peritoneal microvessels, large enough for a significant portion of macromolecules to pass through. The administration of AEBO resulted in the retention of the normal endothelial barrier function during histamine challenge, having prevented the leakage of approximately 99% of the Evans blue dye into the peritoneal cavity. Based on these outcomes, it was demonstrated that AEBO displayed significant antihistamine activity, through inhibition of the vascular permeability processes. This could also be related to the suppression of other permeability-regulating molecules that lead to inflammation.
Vascular endothelial growth factors (VEGFs) are known as key regulators of permeability and binding to their receptors trigger an increase in vascular permeability . Upregulation and downregulation of VEGF expression contributes to abnormal angiogenesis indirectly leading to vascular hyperpermeability . Furthermore, overproduction of VEGF also contributes to progression to other diseases such as coronary disease  and cancer . Ghosh and colleagues  demonstrated that histamine enhanced the production of VEGF during acute inflammation. VEGF release and its above-mentioned effects on vascular permeability and cellular infiltration could contribute to edema formation. Thus, it is very important to regulate VEGF production in cells either by suppression when it is overproduced or vice versa. Our results showed that the oral administration of AEBO in rats decreased the histamine-induced VEGF production, indicating that AEBO may have the potential to regulate vascular permeability by monitoring the expression of VEGF.
Nitric oxide (NO) is a signaling molecule that is synthesized from L-arginine by NO synthase . It is well recognized that NO plays an important role in maintaining the normal physiological function of vascular tissues. It has been previously reported that histamine increased vascular permeability by activating NO production . In addition, Mayhan  also demonstrated that nitric oxide was involved in increased macromolecular extravasation induced by histamine in the hamster cheek pouch. In addition, endothelial nitric oxide synthase (eNOS) was found to play a major role in vascular leakage during acute inflammation in vivo. Thus, suppression of NO production may help reduce acute inflammation. From the present study, it was observed that more than 50% of the NO elevation caused by histamine could be alleviated by AEBO. This further supports its action as an anti-inflammatory agent.
Raga and colleagues  successfully isolated ishwarane, phytol, polyprenol and a mixture of stigmasterol and sitosterol from the dichloromethane extract of air-dried leaves of B. orellana. The current GC-MS analysis revealed six known chemical constituents. However, based on the literature, only four of them are known to exhibit pharmacological activity. Acetic acid is an organic acid that has been reported to possess antifungal  and antibacterial properties . Pentanoic acid (valeric acid) is a sedative, anticonvulsant and mood-stabilizing agent ; whereas phenol was reported to have anesthetic/analgesic  and antiseptic  activities. Benzoic acid possesses antibacterial  and antifungal properties . As for their anti-inflammatory contribution, a low concentration of acetic acid (0.3 mg/mL) has been shown to inhibit histamine release from guinea pig lung mast cells when stimulated by both antigen (ovalbumin) and ionophore A23187 . It is known that allergic reactions develop from large inflammatory responses caused by the release of mediators, including histamine, during degranulation of mast cells. There is also evidence of histamine itself acting as an inducer of mast cell degranulation . This could have happened in our rat model, where histamine was injected into animals to induce inflammation.
All of these constituents may or may not play an important role in the anti-inflammatory activity. Nonetheless, the possibility of the minor compounds exhibiting anti-inflammatory properties cannot be excluded.
Our results confirmed that the aqueous extract of B. orellana had antihistamine activities, as demonstrated by the suppression of increased vascular permeability reflected in the decreased paw volume and Evans blue dye leakage. It appeared that this permeability modulation by AEBO also involved the reduction of biochemical mediators such as NO and VEGF. We considered that the active principle contained in the aqueous extract may play a role in its anti-inflammatory activity. Whether or not it acts by stabilizing mast cells remains to be elucidated.
This research project was funded by the Fundamental Research Grant Scheme (Project No. 04-01-07-100FR) from the Ministry of Higher Education, Malaysia. The funding source has no involvement in the study design, the collection, analysis and interpretation of data, in the writing of the article or in the decision to submit the article for publication. We would also like to thank Lee Han Keng, Cheng Xiao Qi and Chiong Hoe Siong for their assistance in experiments.
YYK, ZAZ, AAK, MNS, GECL and ZA participated in the design of the research. YYK carried out the experiments, analyzed the data and wrote the paper. ZA provided funding and supervised the study. All authors read and approved the final manuscript.