Daily Archives: November 12, 2016

Liberal Warren throws down gauntlet to President-elect …

Posted: November 12, 2016 at 5:28 pm

By Lisa Lambert | WASHINGTON

WASHINGTON U.S. Democrats' liberal firebrand, Senator Elizabeth Warren, threw down the gauntlet to President-elect Donald Trump on Thursday, telling labor union members there are financial and social issues where her party will fight him and continuing to blast the Republican.

Battling bigotry is the first job for Democrats after the election, said Warren, of Massachusetts, giving a sense of how her party will operate now that it no longer controls the White House and remains the minority in both chambers of Congress.

"We will fight back against attacks on Latinos, African Americans, women, Muslims, immigrants, disabled Americans - on anyone," said Warren, who sparred frequently over Twitter with Trump and criticized him on the campaign trail in the weeks leading up to Tuesday's election. "Whether Donald Trump sits in a glass tower or sits in the White House, we will not give an inch on this, not now, not ever."

She said Trump had "encouraged a toxic stew of hatred and fear" and during the campaign "regularly made statements that undermined core values of our democracy."

In the speech to the AFL-CIO labor federation, Warren also said Democrats will resist attempts to loosen financial regulation, "gut" the Dodd-Frank Wall Street reform law and eliminate the Consumer Financial Protection Bureau (CFPB).

"If Trump and the Republican Party try to turn loose the big banks and financial institutions so they can once again gamble with our economy and bring it all crashing down, then we will fight them every step of the way," she said.

Warren did highlight areas of agreement. She said "count me in" on Trump's support of a new Glass-Steagall law to separate investment and retail banking, reforming trade deals, maintaining Social Security benefits, helping on childcare and college costs and rebuilding infrastructure.

Warren rose to lead the liberal wing of the party during the 2007-2009 financial crisis. After Republicans blocked President Barack Obama's attempt to appoint her as the first director of the CFPB, she won a seat in Congress.

In 2015, progressive groups and a political action committee pressed her to run for president. Since Trump's victory on Tuesday, many have already renewed their calls, for the 2020 presidential election.

(Reporting by Lisa Lambert; Editing by Meredith Mazzilli)

WASHINGTON/MARRAKESH, Morocco Donald Trump is seeking quick ways of withdrawing from a global agreement to limit climate change, a source on his transition team said, defying widening international backing for the plan to cut greenhouse gas emissions.

WASHINGTON Congressional Republicans are looking for the quickest ways to tear down Obamacare following Donald Trump's election as U.S. president, including rapidly confirming a new health secretary who could recast regulations while waiting for lawmakers to pass sweeping repeal legislation.

ANKARA Turkey warned its citizens about travel to the United States on Saturday in response to what the foreign ministry called increasingly violent protests against President-elect Donald Trump.

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Financial Independence Academy – Sign Up Today!

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Offshore company – Wikipedia

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The term offshore company or offshore corporation is used in at least two distinct and different ways. An offshore company may be a reference to:

The former use (companies formed in offshore jurisdictions) is probably the more common usage of the term. In isolated instances the term can also be used in reference to companies with offshore oil and gas operations.

In relation to companies and similar entities which are incorporated in offshore jurisdictions,[3] the use of both the words "offshore" and "company" can be varied in application.

The extent to which a jurisdiction is regarded as offshore is often a question of perception and degree.[4] Classic tax haven countries such as Bermuda, British Virgin Islands and the Cayman Islands are quintessentially offshore jurisdictions, and companies incorporated in those jurisdictions are invariably labelled as offshore companies. Thereafter there are certain small intermediate countries or areas such as Hong Kong and Singapore (sometimes referred to as "mid-shore" jurisdictions) which, whilst having oversized financial centres, are not zero tax regimes. Finally, there are classes of industrialised economies which can be used as part of tax mitigation structures, including countries like Ireland, the Netherlands and even the United Kingdom, particularly in commentary relating to corporate inversion. Furthermore, in Federal systems, states which operate like a classic offshore centre can result in corporations formed there being labelled as offshore, even if they form part of the largest economy in the world (for example, Delaware in the United States).

Similarly, the term "company" is used loosely, and at its widest can be taken to refer to any type of artificial entity, including not just corporations and companies, but potentially also LLCs, LPs, LLPs, and sometimes partnerships or even offshore trusts.

Historically, offshore companies were broadly divided into two categories. On the one hand were companies which were statutorily exempt from taxation in their jurisdiction of registration provided that they did not undertake business with persons resident in that jurisdiction. Such companies were usually called International Business Companies, or IBCs. Such companies were largely popularized by the British Virgin Islands, but the model was copied widely. However, in the early 2000s the OECD launched a global initiative to prevent "ring fencing" of taxation in this manner, and many leading jurisdictions (including the British Virgin Islands and Gibraltar) repealed their International Business Companies legislation. But IBCs are still incorporated in a number of jurisdictions today including Anguilla and Panama.

Separately from IBCs, there are countries which operate tax regimes which broadly achieve the same effect: so long as the company's activities are carried on overseas, and none of the profits are repatriated, the company is not subject to taxation in its home jurisdiction. Where the home jurisdiction is regarded as an offshore jurisdiction, such companies are commonly regarded as offshore companies. Examples of this include Hong Kong and Uruguay. However, these tax regimes are not limited to conventional offshore jurisdictions: the United Kingdom operates on broadly similar principles in relation to taxation of companies.

Separately there are offshore jurisdictions which simply do not impose any form of taxation on companies, and so their companies are de facto tax exempt. Historically the best example of these countries were the Cayman Islands and Bermuda,[5] although other countries such as the British Virgin Islands[6] have now moved to this model. These could arguably fit into either of the previous two categories,depending on the fiscal point of view involved.

Although all offshore companies differ to a degree depending upon the corporate law in the relevant jurisdiction, all offshore companies tend to enjoy certain core characteristics:

The absence of taxation or regulation in the home jurisdiction does not of course exempt the relevant company from taxation or regulation abroad. For example, Michael Kors Holdings Limited is incorporated in the British Virgin Islands, but is listed on the New York Stock Exchange, where it is subject both the U.S. taxation and to financial regulation by the U.S. Securities and Exchange Commission.

Another common characteristic of offshore companies is the limited amount of information available to the public. This varies from jurisdiction to jurisdiction. At one end of the scale, in the Cayman Islands and Delaware, there is virtually no publicly available information. But at the other end of the scale, in Hong Kong companies file annual returns with particulars of directors, shareholders and annual accounts. However, even in jurisdictions where there is relatively little information available to the public as of right, most jurisdictions have laws which permit law enforcement authorities (either locally or from overseas) to have access to relevant information,[8] and in some cases, private individuals.[9]

In relation to flexible corporate law, most offshore jurisdictions will normally remove corporate fetters such as thin capitalisation rules, financial assistance rules, and limitations on corporate capacity and corporate benefit. A number have also removed or watered down rules relating to maintenance of capital or restrictions on payment of dividends. Beyond the common themes, a number of jurisdictions have also enacted special corporate provisions to try and attract business through offering corporate mechanisms that allow complex business transactions or reorganisations to occur more smoothly.[10]

Offshore companies are used for a variety of commercial and private purposes, some legitimate and economically beneficial, whilst others may be harmful or even criminal. Allegations are frequently made in the press about offshore companies being used for money laundering, tax evasion, fraud, and other forms of white collar crime. Offshore companies are also used in a wide variety of commercial transactions from generic holding companies, to joint ventures and listing vehicles. Offshore companies are also used widely in connection with private wealth for tax mitigation and privacy. The use of offshore companies, particularly in tax planning, has become controversial in recent years, and a number of high-profile companies have ceased using offshore entities in their group structure as a result of public campaigns for such companies to pay their "fair share" of Government taxes.[11]

Detailed information in relation to the use of offshore companies is notoriously difficult to come by because of the opaque nature of much of the business (and because, in many cases, the companies are used specifically to preserve the confidentiality of a transaction or individual). It is a commonly held view that most uses of offshore companies are driven by tax mitigation and/or regulatory arbitrage, although there are some suggestions that the amount of tax structuring may be less than commonly thought.[12] Other commonly cited legitimate uses of offshore companies include uses as joint ventures,[13] financing SPVs, stock market listing vehicles, holding companies and asset holding structures, and trading vehicles.

Intermediate uses of offshore companies (i.e. uses which might be considered legitimate or illegitimate depending upon a particular person's view of legitimacy of globalisation and tax planning) include uses as investment funds and private wealth holding vehicles.

The alternative use of the phrase offshore company, being a business or part of a business which uses offshoring as part of its business process, is less common, and is often used as a lazy shorthand way of saying that the relevant business engages in offshoring.

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High Seas Fleet – Wikipedia

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The High Seas Fleet (Hochseeflotte) was the battle fleet of the German Imperial Navy and saw action during the First World War. The formation was created in February 1907, when the Home Fleet (Heimatflotte) was renamed as the High Seas Fleet. Admiral Alfred von Tirpitz was the architect of the fleet; he envisioned a force powerful enough to challenge the Royal Navy's predominance. Kaiser Wilhelm II, the German Emperor, championed the fleet as the instrument by which he would seize overseas possessions and make Germany a global power. By concentrating a powerful battle fleet in the North Sea while the Royal Navy was required to disperse its forces around the British Empire, Tirpitz believed Germany could achieve a balance of force that could seriously damage British naval hegemony. This was the heart of Tirpitz's "Risk Theory," which held that Britain would not challenge Germany if the latter's fleet posed such a significant threat to its own.

The primary component of the Fleet was its battleships, typically organized in eight-ship squadrons, though it also contained various other formations, including the I Scouting Group. At its creation in 1907, the High Seas Fleet consisted of two squadrons of battleships, and by 1914, a third squadron had been added. The dreadnought revolution in 1906 greatly affected the composition of the fleet; the twenty-four pre-dreadnoughts in the fleet were rendered obsolete and required replacement. Enough dreadnoughts for two full squadrons were completed by the outbreak of war in mid 1914; the eight most modern pre-dreadnoughts were used to constitute a third squadron. Two additional squadrons of older vessels were mobilized at the onset of hostilities, though by the end of the conflict, these formations were disbanded.

The fleet conducted a series of sorties into the North Sea during the war designed to lure out an isolated portion of the numerically superior British Grand Fleet. These operations frequently used the fast battlecruisers of the I Scouting Group to raid the British coast as the bait for the Royal Navy. These operations culminated in the Battle of Jutland, on 31 May1 June 1916, where the High Seas Fleet confronted the whole of the Grand Fleet. The battle was inconclusive, but the British won strategically, as it convinced Admiral Reinhard Scheer, the German fleet commander, that even a highly favorable outcome to a fleet action would not secure German victory in the war. Scheer and other leading admirals therefore advised the Kaiser to order a resumption of the unrestricted submarine warfare campaign. The primary responsibility of the High Seas Fleet in 1917 and 1918 was to secure the German naval bases in the North Sea for U-boat operations. Nevertheless, the fleet continued to conduct sorties into the North Sea and detached units for special operations in the Baltic Sea against the Russian Baltic Fleet. Following the German defeat in November 1918, the Allies interned the bulk of the High Seas Fleet in Scapa Flow, where it was ultimately scuttled by its crews in June 1919, days before the belligerents signed the Treaty of Versailles.

In 1898, Admiral Alfred von Tirpitz became the State Secretary for the Imperial Navy Office (ReichsmarineamtRMA);[1] Tirpitz was an ardent supporter of naval expansion. During a speech in support of the First Naval Law on 6 December 1897, Tirpitz stated that the navy was "a question of survival" for Germany.[2] He also viewed Great Britain, with its powerful Royal Navy, as the primary threat to Germany. In a discussion with the Kaiser during his first month in his post as State Secretary, he stated that "for Germany the most dangerous naval enemy at present is England."[3] Tirpitz theorized that an attacking fleet would require a 33percent advantage in strength to achieve victory, and so decided that a 2:3 ratio would be required for the German navy. For a final total of 60 German battleships, Britain would be required to build 90 to meet the 2:3 ratio envisioned by Tirpitz.[3]

The Royal Navy had heretofore adhered to the so-called "two-power standard," first formulated in the Naval Defence Act of 1889, which required a larger fleet than those of the next two largest naval powers combined.[4] The crux of Tirpitz's "risk theory" was that by building a fleet to the 2:3 ratio, Germany would be strong enough that even in the event of a British naval victory, the Royal Navy would incur damage so serious as to allow the third-ranked naval power to rise to preeminence. Implicit in Tirpitz's theory was the assumption that the British would adopt an offensive strategy that would allow the Germans to use mines and submarines to even the numerical odds before fighting a decisive battle between Heligoland and the Thames. Tirpitz in fact believed Germany would emerge victorious from a naval struggle with Britain, as he believed Germany to possess superior ships manned by better-trained crews, more effective tactics, and led by more capable officers.[3]

In his first program, Tirpitz envisioned a fleet of nineteen battleships, divided into two eight-ship squadrons, one ship as a flagship, and two in reserve. The squadrons were further divided into four-ship divisions. This would be supported by the eight Siegfried- and Odinclasses of coastal defense ships, six large and eighteen small cruisers, and twelve divisions of torpedo boats, all assigned to the Home Fleet (Heimatflotte).[5] This fleet was secured by the First Naval Law, which passed in the Reichstag on 28 March 1898.[6] Construction of the fleet was to be completed by 1 April 1904. Rising international tensions, particularly as a result of the outbreak of the Boer War in South Africa and the Boxer Rebellion in China, allowed Tirpitz to push through an expanded fleet plan in 1900. The Second Naval Law was passed on 14 June 1900; it doubled the size of the fleet to 38 battleships and 20 large and 38 small cruisers. Tirpitz planned an even larger fleet. As early as September 1899, he had informed the Kaiser that he sought at least 45 battleships, and potentially might secure a third double-squadron, for a total strength of 48 battleships.[7]

During the initial period of German naval expansion, Britain did not feel particularly threatened.[6] The Lords of the Admiralty felt the implications of the Second Naval Law were not a significantly more dangerous threat than the fleet set by the First Naval Law; they believed it was more important to focus on the practical situation rather than speculation on future programs that might easily be reduced or cut entirely. Segments of the British public, however, quickly seized on the perceived threat posed by the German construction programs.[8] Despite their dismissive reaction, the Admiralty resolved to surpass German battleship construction. Admiral John Fisher, who became the First Sea Lord and head of the Admiralty in 1904, introduced sweeping reforms in large part to counter the growing threat posed by the expanding German fleet. Training programs were modernized, old and obsolete vessels were discarded, and the scattered squadrons of battleships were consolidated into four main fleets, three of which were based in Europe. Britain also made a series of diplomatic arrangements, including an alliance with Japan that allowed a greater concentration of British battleships in the North Sea.[9]

Fisher's reforms caused serious problems for Tirpitz's plans; he counted on a dispersal of British naval forces early in a conflict that would allow Germany's smaller but more concentrated fleet to achieve a local superiority. Tirpitz could also no longer depend on the higher level of training in both the German officer corps and the enlisted ranks, nor the superiority of the more modern and homogenized German squadrons over the heterogeneous British fleet. In 1904, Britain signed the Entente cordiale with France, Britain's primary naval rival. The destruction of two Russian fleets during the Russo-Japanese War in 1905 further strengthened Britain's position, as it removed the second of her two traditional naval rivals.[10] These developments allowed Britain to discard the "two power standard" and focus solely on out-building Germany. In October 1906, Admiral Fisher stated "our only probable enemy is Germany. Germany keeps her whole Fleet always concentrated within a few hours of England. We must therefore keep a Fleet twice as powerful concentrated within a few hours of Germany."[11]

The most damaging blow to Tirpitz's plan came with the launch of HMSDreadnought in February 1906. The new battleship, armed with a main battery of ten 12-inch (30cm) guns, was considerably more powerful than any battleship afloat. Ships capable of battle with Dreadnought would need to be significantly larger than the old pre-dreadnoughts, which increased their cost and necessitated expensive dredging of canals and harbors to accommodate them. The German naval budget was already stretched thin; without new funding, Tirpitz would have to abandon his challenge to Britain.[12] As a result, Tirpitz went before the Reichstag in May 1906 with a request for additional funding. The First Amendment to the Second Naval Law was passed on 19 May and appropriated funding for the new battleships, as well as for the dredging required by their increased size.[6]

The Reichstag passed a second amendment to the Naval Law in March 1908 to provide an additional billion marks to cope with the growing cost of the latest battleships. The law also reduced the service life of all battleships from 25 to 20 years, which allowed Tirpitz to push for the replacement of older vessels earlier. A third and final amendment was passed in May 1912 represented a compromise between Tirpitz and moderates in parliament. The amendment authorized three new battleships and two light cruisers. The amendment called for the High Seas Fleet to be equipped with three squadrons of eight battleships each, one squadron of eight battlecruisers, and eighteen light cruisers. Two 8-ship squadrons would be placed in reserve, along with two armored and twelve light cruisers.[13] By the outbreak of war in August 1914, only one eight-ship squadron of dreadnoughtsthe I Battle Squadronhad been assembled with the Nassau and Helgoland-classbattleships. The second squadron of dreadnoughtsthe III Battle Squadronwhich included four of the Kaiser-classbattleships, was only completed when the four Knig-classbattleships entered service by early 1915.[14] As a result, the third squadronthe II Battle Squadronremained composed of pre-dreadnoughts through 1916.[15]

Before the 1912 naval law was passed, Britain and Germany attempted to reach a compromise with the Haldane Mission, led by the British War Minister Richard Haldane. The arms reduction mission ended in failure, however, and the 1912 law was announced shortly thereafter. The Germans were aware at as early as 1911, the Royal Navy had abandoned the idea of a decisive battle with the German fleet, in favor of a distant blockade at the entrances to the North Sea, which the British could easily control due to their geographical position. There emerged the distinct possibility that the German fleet would be unable to force a battle on its own terms, which would render it militarily useless. When the war came in 1914, the British did in fact adopt this strategy. Coupled with the restrictive orders of the Kaiser, who preferred to keep the fleet intact to be used as a bargaining chip in the peace settlements, the ability of the High Seas Fleet to affect the military situation was markedly reduced.[16]

The German Navy's pre-war planning held that the British would be compelled to mount either a direct attack on the German coast to defeat the High Seas Fleet, or to put in place a close blockade. Either course of action would permit the Germans to whittle away at the numerical superiority of the Grand Fleet with submarines and torpedo boats. Once a rough equality of forces could be achieved, the High Seas Fleet would be able to attack and destroy the British fleet.[17] Implicit in Tirpitz's strategy was the assumption that German vessels were better-designed, had better-trained crews, and would be employed with superior tactics. In addition, Tirpitz assumed that Britain would not be able to concentrate its fleet in the North Sea, owing to the demands of its global empire. At the start of a conflict between the two powers, the Germans would therefore be able to attack the Royal Navy with local superiority.[18]

The British, however, did not accommodate Tirpitz's projections; from his appointment as the First Sea Lord in 1904, Fisher began a major reorganization of the Royal Navy. He concentrated British battleship strength in home waters, launched the Dreadnought revolution, and introduced rigorous training for the fleet personnel.[19] In 1912, the British concluded a joint defense agreement with France that allowed the British to concentrate in the North Sea while the French defended the Mediterranean.[20] Worse still, the British began developing the strategy of the distant blockade of Germany starting in 1904;[21] this removed the ability of German light craft to reduce Britain's superiority in numbers and essentially invalidated German naval planning before the start of World War I.[22]

The primary base for the High Seas Fleet in the North Sea was Wilhelmshaven on the western side of the Jade Bight; the port of Cuxhaven, located on the mouth of the Elbe, was also a major base in the North Sea. The island of Heligoland provided a fortified forward position in the German Bight.[23]Kiel was the most important base in the Baltic, which supported the forward bases at Pillau and Danzig.[24] The Kaiser Wilhelm Canal through Schleswig-Holstein connected the Baltic and North Seas and allowed the German Navy to quickly shift naval forces between the two seas.[25] In peacetime, all ships on active duty in the High Seas Fleet were stationed in Wilhelmshaven, Kiel, or Danzig.[26] Germany possessed only one major overseas base, at Kiautschou in China,[27] where the East Asia Squadron was stationed.[28]

Steam ships of the period, which burned coal to fire their boilers, were naturally tied to coaling stations in friendly ports. The German Navy lacked sufficient overseas bases for sustained operations, even for single ships operating as commerce raiders.[29] The Navy experimented with a device to transfer coal from colliers to warships while underway in 1907, though the practice was not put into general use.[30] Nevertheless, German capital ships had a cruising range of at least 4,000nmi (7,400km; 4,600mi),[31] more than enough to operate in the Atlantic Ocean.[Note 1]

In 1897, the year Tirpitz came to his position as State Secretary of the Navy Office, the Imperial Navy consisted of a total of around 26,000 officers, petty officers, and enlisted men of various ranks, branches, and positions. By the outbreak of war in 1914, this had increased significantly to about 80,000 officers, petty officers, and men.[35] Capital ships were typically commanded by a Kapitn zur See (Captain at Sea) or Korvettenkapitn (corvette captain).[26] Each of these ships typically had a total crew in excess of 1,000 officers and men;[31] the light cruisers that screened for the fleet had crew sizes between 300 and 550.[36] The fleet torpedo boats had crews of about 80 to 100 officers and men, though some later classes approached 200.[37]

In early 1907, enough battleshipsof the Braunschweig and Deutschlandclasseshad been constructed to allow for the creation of a second full squadron.[38] On 16 February 1907,[39] Kaiser Wilhelm renamed the Home Fleet the High Seas Fleet. Admiral Prince Heinrich of Prussia, Wilhelm II's brother, became the first commander of the High Seas Fleet; his flagship was SMSDeutschland.[38] While in a peace-time footing, the Fleet conducted a routine pattern of training exercises, with individual ships, with squadrons, and with the combined fleet, throughout the year. The entire fleet conducted several cruises into the Atlantic Ocean and the Baltic Sea.[40] Prince Henry was replaced in late 1909 by Vice Admiral Henning von Holtzendorff, who served until April 1913. Vice Admiral Friedrich von Ingenohl, who would command the High Seas Fleet in the first months of World War I, took command following the departure of Vice Admiral von Holtzendorff.[41]SMSFriedrich der Grosse replaced Deutschland as the fleet flagship on 2 March 1913.[42]

Despite the rising international tensions following the assassination of Archduke Franz Ferdinand on 28 June, the High Seas Fleet began its summer cruise to Norway on 13 July. During the last peacetime cruise of the Imperial Navy, the fleet conducted drills off Skagen before proceeding to the Norwegian fjords on 25 July. The following day the fleet began to steam back to Germany, as a result of Austria-Hungary's ultimatum to Serbia. On the 27th, the entire fleet assembled off Cape Skudenes before returning to port, where the ships remained at a heightened state of readiness.[42] War between Austria-Hungary and Serbia broke out the following day, and in the span of a week all of the major European powers had joined the conflict.[43]

The High Seas Fleet conducted a number of sweeps and advances into the North Sea. The first occurred on 23 November 1914, though no British forces were encountered. Admiral von Ingenohl, the commander of the High Seas Fleet, adopted a strategy in which the battlecruisers of Rear Admiral Franz von Hipper's I Scouting Group raided British coastal towns to lure out portions of the Grand Fleet where they could be destroyed by the High Seas Fleet.[44] The raid on Scarborough, Hartlepool and Whitby on 1516 December 1914 was the first such operation.[45] On the evening of 15 December, the German battle fleet of some twelve dreadnoughts and eight pre-dreadnoughts came to within 10nmi (19km; 12mi) of an isolated squadron of six British battleships. However, skirmishes between the rival destroyer screens in the darkness convinced von Ingenohl that he was faced with the entire Grand Fleet. Under orders from the Kaiser to avoid risking the fleet unnecessarily, von Ingenohl broke off the engagement and turned the fleet back toward Germany.[46]

Following the loss of SMSBlcher at the Battle of Dogger Bank in January 1915, the Kaiser removed Admiral von Ingenohl from his post on 2 February. Admiral Hugo von Pohl replaced him as commander of the fleet.[47] Admiral von Pohl conducted a series of fleet advances in 1915; in the first one on 2930 March, the fleet steamed out to the north of Terschelling and returned without incident. Another followed on 1718 April, where the fleet covered a mining operation by the II Scouting Group. Three days later, on 2122 April, the High Seas Fleet advanced towards the Dogger Bank, though again failed to meet any British forces.[48] Another sortie followed on 2930 May, during which the fleet advanced as far as Schiermonnikoog before being forced to turn back by inclement weather. On 10 August, the fleet steamed to the north of Heligoland to cover the return of the auxiliary cruiser Meteor. A month later, on 1112 September, the fleet covered another mine-laying operation off the Swarte Bank. The last operation of the year, conducted on 2324 October, was an advance without result in the direction of Horns Reef.[48]

Vice Admiral Reinhard Scheer became Commander in chief of the High Seas Fleet on 18 January 1916 when Admiral von Pohl became too ill to continue in that post.[49] Scheer favored a much more aggressive policy than that of his predecessor, and advocated greater usage of U-boats and zeppelins in coordinated attacks on the Grand Fleet; Scheer received approval from the Kaiser in February 1916 to carry out his intentions.[50] Scheer ordered the fleet on sweeps of the North Sea on 26 March, 23 April, and 2122 April. The battlecruisers conducted another raid on the English coast on 2425 April, during which the fleet provided distant support.[51] Scheer planned another raid for mid-May, but the battlecruiser Seydlitz had struck a mine during the previous raid and the repair work forced the operation to be pushed back until the end of the month.[52]

Admiral Scheer's fleet, composed of 16 dreadnoughts, six pre-dreadnoughts, six light cruisers, and 31 torpedo boats departed the Jade early on the morning of 31 May. The fleet sailed in concert with Hipper's five battlecruisers and supporting cruisers and torpedo boats.[53] The British navy's Room 40 had intercepted and decrypted German radio traffic containing plans of the operation. The Admiralty ordered the Grand Fleet, totaling some 28 dreadnoughts and 9 battlecruisers, to sortie the night before in order to cut off and destroy the High Seas Fleet.[54]

At 16:00 UTC, the two battlecruiser forces encountered each other and began a running gun fight south, back towards Scheer's battle fleet.[55] Upon reaching the High Seas Fleet, Vice Admiral David Beatty's battlecruisers turned back to the north to lure the Germans towards the rapidly approaching Grand Fleet, under the command of Admiral John Jellicoe.[56] During the run to the north, Scheer's leading ships engaged the Queen Elizabeth-class battleships of the 5th Battle Squadron.[57] By 18:30, the Grand Fleet had arrived on the scene, and was deployed into a position that would cross Scheer's "T" from the northeast. To extricate his fleet from this precarious position, Scheer ordered a 16-point turn to the south-west.[58] At 18:55, Scheer decided to conduct another 16-point turn to launch an attack on the British fleet.[59]

This maneuver again put Scheer in a dangerous position; Jellicoe had turned his fleet south and again crossed Scheer's "T."[60] A third 16-point turn followed; Hipper's mauled battlecruisers charged the British line to cover the retreat.[61] Scheer then ordered the fleet to adopt the night cruising formation, which was completed by 23:40.[62] A series of ferocious engagements between Scheer's battleships and Jellicoe's destroyer screen ensued, though the Germans managed to punch their way through the destroyers and make for Horns Reef.[63] The High Seas Fleet reached the Jade between 13:00 and 14:45 on 1 June; Scheer ordered the undamaged battleships of the I Battle Squadron to take up defensive positions in the Jade roadstead while the Kaiser-class battleships were to maintain a state of readiness just outside Wilhelmshaven.[64] The High Seas Fleet had sunk more British vessels than the Grand Fleet had sunk German, though Scheer's leading battleships had taken a terrible hammering. Several capital ships, including SMSKnig, which had been the first vessel in the line, and most of the battlecruisers, were in drydock for extensive repairs for at least two months. On 1 June, the British had twenty-four capital ships in fighting condition, compared to only ten German warships.[65]

By August, enough warships had been repaired to allow Scheer to undertake another fleet operation on 1819 August. Due to the serious damage incurred by Seydlitz and SMSDerfflinger and the loss of SMSLtzow at Jutland, the only battlecruisers available for the operation were SMSVon der Tann and SMSMoltke, which were joined by SMSMarkgraf, SMSGrosser Kurfrst, and the new battleship SMSBayern.[66] Scheer turned north after receiving a false report from a zeppelin about a British unit in the area.[48] As a result, the bombardment was not carried out, and by 14:35, Scheer had been warned of the Grand Fleet's approach and so turned his forces around and retreated to German ports.[67] Another fleet sortie took place on 1819 October 1916 to attack enemy shipping east of Dogger Bank. Despite being forewarned by signal intelligence, the Grand Fleet did not attempt to intercept. The operation was however cancelled due to poor weather after the cruiser Mnchen was torpedoed by the British submarine HMSE38.[68] The fleet was reorganized on 1 December;[48] the four Knig-classbattleships remained in the III Squadron, along with the newly commissioned Bayern, while the five Kaiser-class ships were transferred to the IV Squadron.[69] In March 1917 the new battleship Baden, built to serve as fleet flagship, entered service;[70] on the 17th, Scheer hauled down his flag from Friedrich der Grosse and transferred it to Baden.[48]

The war, now in its fourth year, was by 1917 taking its toll on the crews of the ships of the High Seas Fleet. Acts of passive resistance, such as the posting of anti-war slogans in the battleships SMSOldenburg and SMSPosen in January 1917, began to appear.[71] In June and July, the crews began to conduct more active forms of resistance. These activities included work refusals, hunger strikes, and taking unauthorized leave from their ships.[72] The disruptions came to a head in August, when a series of protests, anti-war speeches, and demonstrations resulted in the arrest of dozens of sailors.[73] Scheer ordered the arrest of over 200 men from the battleship Prinzregent Luitpold, the center of the anti-war activities. A series of courts-martial followed, which resulted in 77 guilty verdicts; nine men were sentenced to death for their roles, though only two men, Albin Kbis and Max Reichpietsch, were executed.[74]

In early September 1917, following the German conquest of the Russian port of Riga, the German navy decided to eliminate the Russian naval forces that still held the Gulf of Riga. The Navy High Command (Admiralstab) planned an operation, codenamed Operation Albion, to seize the Baltic island of sel, and specifically the Russian gun batteries on the Sworbe Peninsula.[75] On 18 September, the order was issued for a joint operation with the army to capture sel and Moon Islands; the primary naval component was to comprise its flagship, Moltke, and the III and IVBattle Squadrons of the High Seas Fleet.[76] The operation began on the morning of 12 October, when Moltke and the IIISquadron ships engaged Russian positions in Tagga Bay while the IVSquadron shelled Russian gun batteries on the Sworbe Peninsula on sel.[77]By 20 October, the fighting on the islands was winding down; Moon, sel, and Dag were in German possession. The previous day, the Admiralstab had ordered the cessation of naval actions and the return of the dreadnoughts to the High Seas Fleet as soon as possible.[78]

Admiral Scheer had used light surface forces to attack British convoys to Norway beginning in late 1917. As a result, the Royal Navy attached a squadron of battleships to protect the convoys, which presented Scheer with the possibility of destroying a detached squadron of the Grand Fleet. The operation called for Hipper's battlecruisers to attack the convoy and its escorts on 23 April while the battleships of the High Seas Fleet stood by in support. On 22 April, the German fleet assembled in the Schillig Roads outside Wilhelmshaven and departed the following morning.[79] Despite the success in reaching the convoy route undetected, the operation failed due to faulty intelligence. Reports from U-boats indicated to Scheer that the convoys sailed at the start and middle of each week, but a west-bound convoy had left Bergen on Tuesday the 22nd and an east-bound group left Methil, Scotland, on the 24th, a Thursday. As a result, there was no convoy for Hipper to attack.[80] Beatty sortied with a force of 31 battleships and four battlecruisers, but was too late to intercept the retreating Germans. The Germans reached their defensive minefields early on 25 April, though approximately 40nmi (74km; 46mi) off Heligoland Moltke was torpedoed by the submarine E42; she successfully returned to port.[81]

A final fleet action was planned for the end of October 1918, days before the Armistice was to take effect. The bulk of the High Seas Fleet was to have sortied from their base in Wilhelmshaven to engage the British Grand Fleet; Scheerby now the Grand Admiral (Grossadmiral) of the fleetintended to inflict as much damage as possible on the British navy, in order to retain a better bargaining position for Germany, despite the expected casualties. However, many of the war-weary sailors felt the operation would disrupt the peace process and prolong the war.[82] On the morning of 29 October 1918, the order was given to sail from Wilhelmshaven the following day. Starting on the night of 29 October, sailors on Thringen and then on several other battleships mutinied.[83] The unrest ultimately forced Hipper and Scheer to cancel the operation.[84] When informed of the situation, the Kaiser stated "I no longer have a navy."[85]

Following the capitulation of Germany on November 1918, most of the High Seas Fleet, under the command of Rear Admiral Ludwig von Reuter, were interned in the British naval base of Scapa Flow.[84] Prior to the departure of the German fleet, Admiral Adolf von Trotha made clear to von Reuter that he could not allow the Allies to seize the ships, under any conditions.[86] The fleet rendezvoused with the British light cruiser Cardiff, which led the ships to the Allied fleet that was to escort the Germans to Scapa Flow. The massive flotilla consisted of some 370 British, American, and French warships.[87] Once the ships were interned, their guns were disabled through the removal of their breech blocks, and their crews were reduced to 200 officers and enlisted men on each of the capital ships.[88]

The fleet remained in captivity during the negotiations that ultimately produced the Treaty of Versailles. Von Reuter believed that the British intended to seize the German ships on 21 June 1919, which was the deadline for Germany to have signed the peace treaty. Unaware that the deadline had been extended to the 23rd, Reuter ordered the ships to be sunk at the next opportunity. On the morning of 21 June, the British fleet left Scapa Flow to conduct training maneuvers, and at 11:20 Reuter transmitted the order to his ships.[86] Out of the interned fleet, only one battleship, Baden, three light cruisers, and eighteen destroyers were saved from sinking by the British harbor personnel. The Royal Navy, initially opposed to salvage operations, decided to allow private firms to attempt to raise the vessels for scrapping.[89] Cox and Danks, a company founded by Ernest Cox handled most of the salvage operations, including those of the heaviest vessels raised.[90] After Cox's withdrawal due to financial losses in the early 1930s, Metal Industries Group, Inc. took over the salvage operation for the remaining ships. Five more capital ships were raised, though threeSMS Knig, SMSKronprinz, and SMS Markgrafwere too deep to permit raising. They remain on the bottom of Scapa Flow, along with four light cruisers.[91]

The High Seas Fleet, particularly its wartime impotence and ultimate fate, strongly influenced the later German navies, the Reichsmarine and Kriegsmarine. Former Imperial Navy officers continued to serve in the subsequent institutions, including Admiral Erich Raeder, Hipper's former chief of staff, who became the commander in chief of the Reichsmarine. Raeder advocated long-range commerce raiding by surface ships, rather than constructing a large surface fleet to challenge the Royal Navy, which he viewed to be a futile endeavor. His initial version of Plan Z, the construction program for the Kriegsmarine in the late 1930s, called for large number of P-classcruisers, long-range light cruisers, and reconnaissance forces for attacking enemy shipping, though he was overruled by Adolf Hitler, who advocated a large fleet of battleships.[92]

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What are the Benefits of Mind Uploading? – Lifeboat

Posted: at 5:24 pm

by Lifeboat Foundation Scientific Advisory Board member Michael Anissimov. Overview Universal mind uploading, or universal uploading for short, is the concept, by no means original to me, that the technology of mind uploading will eventually become universally adopted by all who can afford it, similar to the adoption of modern agriculture, hygiene, or living in houses. The concept is rather infrequently discussed, due to a combination of 1) its supposedly speculative nature and 2) its far future time frame. Discussion Before I explore the idea, let me give a quick description of what mind uploading is and why the two roadblocks to its discussion are invalid. Mind uploading would involve simulating a human brain in a computer in enough detail that the simulation becomes, for all practical purposes, a perfect copy and experiences consciousness, just like protein-based human minds. If functionalism is true, like many cognitive scientists and philosophers correctly believe, then all the features of human consciousness that we know and love including all our memories, personality, and sexual quirks would be preserved through the transition. By simultaneously disassembling the protein brain as the computer brain is constructed, only one implementation of the person in question would exist at any one time, eliminating any unnecessary confusion. Still, even if two direct copies are made, the universe wont care you would have simply created two identical individuals with the same memories. The universe cant get confused only you can. Regardless of how perplexed one may be by contemplating this possibility for the first time from a 20th century perspective of personal identity, an upload of you with all your memories and personality intact is no different from you than the person you are today is different than the person you were yesterday when you went to sleep, or the person you were 10-30 seconds ago when quantum fluctuations momentarily destroyed and recreated all the particles in your brain. Regarding objections to talk of uploading, for anyone who 1) buys the silicon brain replacement thought experiment, 2) accepts arguments that the human brain operates at below about 1019 ops/sec, and 3) considers it plausible that 1019 ops/sec computers (plug in whatever value you believe for #2) will become manufactured this century, the topic is clearly worth broaching. Even if its 100 years off, thats just a blink of an eye relative to the entirety of human history, and universal uploading would be something more radical than anything thats occurred with life or intelligence in the entire known history of this solar system. We can afford to stop focusing exclusively on the near future for a potential event of such magnitude. Consider it intellectual masturbation, if you like, or a serious analysis of the near-term future of the human species, if you buy the three points. So, say that mind uploading becomes available as a technology sometime around 2050. If the early adopters dont go crazy and/or use their newfound abilities to turn the world into a totalitarian dictatorship, then they will concisely and vividly communicate the benefits of the technology to their non-uploaded family and friends. If affordable, others will then follow, but the degree of adoption will necessarily depend on whether the process is easily reversible or not. But suppose that millions of people choose to go for it. Effects Widespread uploading would have huge effects. Lets go over some of them in turn 1) Massive economic growth. By allowing human minds to run on substrates that can be accelerated by the addition of computing power, as well as the possibility of spinning off non-conscious daemons to accomplish rote tasks, economic growth at least insofar as it can be accelerated by intelligence and the robotics of 2050 alone will accelerate greatly. Instead of relying upon 1% per year population growth rates, humans might copy themselves or (more conducive to societal diversity) spin off already-mature progeny as quickly as available computing power allows. This could lead to growth rates in human capital of 1,000% per year or far more. More economic growth might ensue in the first year (or month) after uploading than in the entire 250,000 years between the evolution of Homo sapiens and the invention of uploading. The first country that widely adopts the technology might be able to solve global poverty by donating only 0.1% of its annual GDP. 2) Intelligence enhancement. Faster does not necessarily mean smarter. Weak superintelligence is a term sometimes used to describe accelerated intelligence that is not qualitatively enhanced, in contrast with strong superintelligence which is. The road from weak to strong superintelligence would likely be very short. By observing information flows in uploaded human brains, many of the details of human cognition would be elucidated. Running standard compression algorithms over such minds might make them more efficient than blind natural selection could manage, and this extra space could be used to introduce new information-processing modules with additional features. Collectively, these new modules could give rise to qualitatively better intelligence. At the very least, rapid trial-and-error experimentation without the risk of injury would become possible, eventually revealing paths to qualitative enhancements. 3) Greater subjective well-being. Like most other human traits, our happiness set points fall on a bell curve. No matter what happens to us, be it losing our home or winning the lottery, there is a tendency for our innate happiness level to revert back to our natural set point. Some lucky people are innately really happy. Some unlucky people have chronic depression. With uploading, we will be able to see exactly which neural features (happiness centers) correspond to high happiness set points and which dont, by combining prior knowledge with direct experimentation and investigation. This will make it possible for people to reprogram their own brains to raise their happiness set points in a way that biotechnological intervention might find difficult or dangerous. Experimental data and simple observation has shown that high happiness set-point people today dont have any mysterious handicaps, like inability to recognize when their body is in pain, or inappropriate social behavior. They still experience sadness, its just that their happiness returns to a higher level after the sad experience is over. Perennial tropes justifying the value of suffering will lose their appeal when anyone can be happier without any negative side effects. 4) Complete environmental recovery. (Im not just trying to kiss up to greens, I actually care about this.) By spending most of our time as programs running on a worldwide network, we will consume far less space and use less energy and natural resources than we would in a conventional human body. Because our food would be delicious cuisines generated only by electricity or light, we could avoid all the environmental destruction caused by clear-cutting land for farming and the ensuing agricultural runoff. People imagine dystopian futures to involve a lot of homogeneity well, were already here as far as our agriculture is concerned. Land that once had diverse flora and fauna now consists of a few dozen agricultural staples wheat, corn, oats, cattle pastures, factory farms. BORING. By transitioning from a proteinaceous to a digital substrate, well do more for our environment than any amount of conservation ever could. We could still experience this environment by inputting live-updating feeds of the biosphere into a corner of our expansive virtual worlds. Its the best of both worlds, literally virtual and natural in harmony. 5) Escape from direct governance by the laws of physics. Though this benefit sounds more abstract or philosophical, if we were to directly experience it, the visceral nature of this benefit would become immediately clear. In a virtual environment, the programmer is the complete master of everything he or she has editing rights to. A personal virtual sandbox could become ones canvas for creating the fantasy world of their choice. Today, this can be done in a very limited fashion in virtual worlds such as Second Life. (A trend which will continue to the fulfillment of everyones most escapist fantasies, even if uploading is impossible.) Worlds like Second Life are still limited by their system-wide operating rules and their low resolution and bandwidth. Any civilization that develops uploading would surely have the technology to develop virtual environments of great detail and flexibility, right up to the very boundaries of the possible. Anything that can become possible will be. People will be able to experience simulations of the past, travel to far-off stars and planets, and experience entirely novel worldscapes, all within the flickering bits of the worldwide network. 6) Closer connections with other human beings. Our interactions with other people today is limited by the very low bandwidth of human speech and facial expressions. By offering partial readouts of our cognitive state to others, we could engage in a deeper exchange of ideas and emotions. I predict that talking as communication will become pass well engage in much deeper forms of informational and emotional exchange that will make the talking and facial expressions of today seem downright empty and soulless. Spiritualists often talk a lot about connecting closer to one another are they aware that the best way they can go about that would be to contribute to researching neural scanning or brain-computer interfacing technology? Probably not. 7) Last but not least, indefinite lifespans. Here is the one that detractors of uploading are fond of targeting the fact that uploading could lead to practical immortality. Well, it really could. By being a string of flickering bits distributed over a worldwide network, killing you could become extremely difficult. The data and bits of everyone would be intertwined to kill someone, youll either need complete editing privileges of the entire worldwide network, or the ability to blow up the planet. Needless to say, true immortality would be a huge deal, a much bigger deal than the temporary fix of life extension therapies for biological bodies, which will do very little to combat infectious disease or exotic maladies such as being hit by a truck. Conclusion Its obvious that mind uploading would be incredibly beneficial. As stated near the beginning of this post, only three things are necessary for it to be a big deal 1) that you believe a brain could be incrementally replaced with functionally identical implants and retain its fundamental characteristics and identity, 2) that the computational capacity of the human brain is a reasonable number, very unlikely to be more than 1019 ops/sec, and 3) that at some point in the future well have computers that fast. Not so far-fetched. Many people consider these three points plausible, but just arent aware of their implications. If you believe those three points, then uploading becomes a fascinating goal to work towards. From a utilitarian perspective, it practically blows everything else away besides global risk mitigation, as the number of new minds leading worthwhile lives that could be created using the technology would be astronomical. The number of digital minds we could create using the matter on Earth alone would likely be over a quadrillion, more than 2,500 people for every star in the 400 billion star Milky Way. We could make a Galactic Civilization right here on Earth in the late 21st or 22nd century. I can scarcely imagine such a thing, but I can imagine that well be guffawing heartily as how unambitious most human goals were in the year 2010.

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Food supplements – Food Safety – European Commission

Posted: at 5:24 pm

As an addition to a normal diet, food business operators market food supplements, which are concentrated sources of nutrients (or other substances) with a nutritional or physiological effect. Such food supplements can be marketed in dose form, such as pills, tablets, capsules, liquids in measured doses, etc.

The objective of the harmonised rules on those products in Directive 2002/46/EC is to protect consumers against potential health risks from those products and to ensure that they are not provided with misleading information.

With respect to the safety of food supplements, the Directive lays down a harmonised list of vitamins and minerals that may be added for nutritional purposes in food supplements (in Annex I to the Directive). Annex II of the Directive contains a list of permitted sources (vitamin and mineral substances) from which those vitamins and minerals may be manufactured.

This list has been amended by the following Regulations and Directive to include additional substances:

The trade of products containing vitamins and minerals not listed in Annex II has been prohibited from the 1st of August 2005.

Directive 2002/46/EC has been aligned with the new Regulatory Procedure with scrutiny by Regulation (EC) 1137/2008.

Directive 2002/46/EC on food supplements envisages the setting of maximum and minimum amounts of vitamins and minerals in supplements via the Standing Committee on Plants, Animals, Food and Feed ( PAFF Committee) procedure.

The Commission has issued a Discussion Paper on the setting of maximum and minimum amounts for vitamins and minerals in foodstuffs , which identified the main issues to be considered in this exercise and originated a set of Responses.

Although the Commission has consulted extensively with Member States and interested stakeholders on the issue, no proposal has not yet been presented due to the complex nature of the issue and the divergent views that were expressed. All the available data on the potential effects on economic operators and consumers of the setting of maximum amounts of vitamins and minerals in foods, including food supplements, will be taken into account. Every effort will be made to ensure that the maximum amounts set will take into account the concerns expressed by all interested parties.

The EC commissioned a study on the use of substances with nutritional or physiological effects other than vitamins and minerals in food supplements.

Taking into account this study and other available information, the Commission - in accordance with the requirement set out in Article 4(8) of Directive 2002/46/EC on food supplements - has prepared a report to the Council and the European Parliament on the use of substances other than vitamins and minerals in food supplements.

The report is accompanied by two Commission staff working documents.

Member States may, for monitoring purposes, request notification to their competent authority of the placing on the market in their territory of a food supplement product in accordance with Article 10 of the Directive. The list of competent authorities may be found here:

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Human genetics – Wikipedia

Posted: at 5:20 pm

Human Genetics is the study of inheritance as it occurs in human beings. Human genetics encompasses a variety of overlapping fields including: classical genetics, cytogenetics, molecular genetics, biochemical genetics, genomics, population genetics, developmental genetics, clinical genetics, and genetic counseling.

Genes can be the common factor of the qualities of most human-inherited traits. Study of human genetics can be useful as it can answer questions about human nature, understand the diseases and development of effective disease treatment, and understand genetics of human life. This article describes only basic features of human genetics; for the genetics of disorders please see: Medical genetics.

Inheritance of traits for humans are based upon Gregor Mendel's model of inheritance. Mendel deduced that inheritance depends upon discrete units of inheritance, called factors or genes.[1]

Autosomal traits are associated with a single gene on an autosome (non-sex chromosome)they are called "dominant" because a single copyinherited from either parentis enough to cause this trait to appear. This often means that one of the parents must also have the same trait, unless it has arisen due to an unlikely new mutation. Examples of autosomal dominant traits and disorders are Huntington's disease and achondroplasia.

Autosomal recessive traits is one pattern of inheritance for a trait, disease, or disorder to be passed on through families. For a recessive trait or disease to be displayed two copies of the trait or disorder needs to be presented. The trait or gene will be located on a non-sex chromosome. Because it takes two copies of a trait to display a trait, many people can unknowingly be carriers of a disease. From an evolutionary perspective, a recessive disease or trait can remain hidden for several generations before displaying the phenotype. Examples of autosomal recessive disorders are albinism, cystic fibrosis.

X-linked genes are found on the sex X chromosome. X-linked genes just like autosomal genes have both dominant and recessive types. Recessive X-linked disorders are rarely seen in females and usually only affect males. This is because males inherit their X chromosome and all X-linked genes will be inherited from the maternal side. Fathers only pass on their Y chromosome to their sons, so no X-linked traits will be inherited from father to son. Men cannot be carriers for recessive X linked traits, as they only have one X chromosome, so any X linked trait inherited from the mother will show up.

Females express X-linked disorders when they are homozygous for the disorder and become carriers when they are heterozygous. X-linked dominant inheritance will show the same phenotype as a heterozygote and homozygote. Just like X-linked inheritance, there will be a lack of male-to-male inheritance, which makes it distinguishable from autosomal traits. One example of an X-linked trait is CoffinLowry syndrome, which is caused by a mutation in ribosomal protein gene. This mutation results in skeletal, craniofacial abnormalities, mental retardation, and short stature.

X chromosomes in females undergo a process known as X inactivation. X inactivation is when one of the two X chromosomes in females is almost completely inactivated. It is important that this process occurs otherwise a woman would produce twice the amount of normal X chromosome proteins. The mechanism for X inactivation will occur during the embryonic stage. For people with disorders like trisomy X, where the genotype has three X chromosomes, X-inactivation will inactivate all X chromosomes until there is only one X chromosome active. Males with Klinefelter syndrome, who have an extra X chromosome, will also undergo X inactivation to have only one completely active X chromosome.

Y-linked inheritance occurs when a gene, trait, or disorder is transferred through the Y chromosome. Since Y chromosomes can only be found in males, Y linked traits are only passed on from father to son. The testis determining factor, which is located on the Y chromosome, determines the maleness of individuals. Besides the maleness inherited in the Y-chromosome there are no other found Y-linked characteristics.

A pedigree is a diagram showing the ancestral relationships and transmission of genetic traits over several generations in a family. Square symbols are almost always used to represent males, whilst circles are used for females. Pedigrees are used to help detect many different genetic diseases. A pedigree can also be used to help determine the chances for a parent to produce an offspring with a specific trait.

Four different traits can be identified by pedigree chart analysis: autosomal dominant, autosomal recessive, x-linked, or y-linked. Partial penetrance can be shown and calculated form pedigrees. Penetrance is the percentage expressed frequency with which individuals of a given genotype manifest at least some degree of a specific mutant phenotype associated with a trait.

Inbreeding, or mating between closely related organisms, can clearly be seen on pedigree charts. Pedigree charts of royal families often have a high degree of inbreeding, because it was customary and preferable for royalty to marry another member of royalty. Genetic counselors commonly use pedigrees to help couples determine if the parents will be able to produce healthy children.

A karyotype is a very useful tool in cytogenetics. A karyotype is picture of all the chromosomes in the metaphase stage arranged according to length and centromere position. A karyotype can also be useful in clinical genetics, due to its ability to diagnose genetic disorders. On a normal karyotype, aneuploidy can be detected by clearly being able to observe any missing or extra chromosomes.[1]

Giemsa banding, g-banding, of the karyotype can be used to detect deletions, insertions, duplications, inversions, and translocations. G-banding will stain the chromosomes with light and dark bands unique to each chromosome. A FISH, fluorescent in situ hybridization, can be used to observe deletions, insertions, and translocations. FISH uses fluorescent probes to bind to specific sequences of the chromosomes that will cause the chromosomes to fluoresce a unique color.[1]

Genomics refers to the field of genetics concerned with structural and functional studies of the genome.[1] A genome is all the DNA contained within an organism or a cell including nuclear and mitochondrial DNA. The human genome is the total collection of genes in a human being contained in the human chromosome, composed of over three billion nucleotides.[2] In April 2003, the Human Genome Project was able to sequence all the DNA in the human genome, and to discover that the human genome was composed of around 20,000 protein coding genes.

Medical genetics' is the branch of medicine that involves the diagnosis and management of hereditary disorders. Medical genetics is the application of genetics to medical care. It overlaps human genetics, for example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counseling of individuals with genetic disorders would be considered part of medical genetics.

Population genetics is the branch of evolutionary biology responsible for investigating processes that cause changes in allele and genotype frequencies in populations based upon Mendelian inheritance.[3] Four different forces can influence the frequencies: natural selection, mutation, gene flow (migration), and genetic drift. A population can be defined as a group of interbreeding individuals and their offspring. For human genetics the populations will consist only of the human species. The Hardy-Weinberg principle is a widely used principle to determine allelic and genotype frequencies.

In addition to nuclear DNA, humans (like almost all eukaryotes) have mitochondrial DNA. Mitochondria, the "power houses" of a cell, have their own DNA. Mitochondria are inherited from one's mother, and its DNA is frequently used to trace maternal lines of descent (see mitochondrial Eve). Mitochondrial DNA is only 16kb in length and encodes for 62 genes.

The XY sex-determination system is the sex-determination system found in humans, most other mammals, some insects (Drosophila), and some plants (Ginkgo). In this system, the sex of an individual is determined by a pair of sex chromosomes (gonosomes). Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. Males have two distinct sex chromosomes (XY), and are called the heterogametic sex.

Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance. Since humans have many more genes on the X than the Y, there are many more X-linked traits than Y-linked traits. However, females carry two or more copies of the X chromosome, resulting in a potentially toxic dose of X-linked genes.[4]

To correct this imbalance, mammalian females have evolved a unique mechanism of dosage compensation. In particular, by way of the process called X-chromosome inactivation (XCI), female mammals transcriptionally silence one of their two Xs in a complex and highly coordinated manner.[4]

Genetic Chromosomal

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Whole genome sequencing – Wikipedia

Posted: at 5:20 pm

"Genome sequencing" redirects here. For the sequencing only of DNA, see DNA sequencing.

Whole genome sequencing (also known as WGS, full genome sequencing, complete genome sequencing, or entire genome sequencing) is a laboratory process that determines the complete DNA sequence of an organism's genome at a single time. This entails sequencing all of an organism's chromosomal DNA as well as DNA contained in the mitochondria and, for plants, in the chloroplast.

Whole genome sequencing should not be confused with DNA profiling, which only determines the likelihood that genetic material came from a particular individual or group, and does not contain additional information on genetic relationships, origin or susceptibility to specific diseases.[2] Also unlike full genome sequencing, SNP genotyping covers less than 0.1% of the genome. Almost all truly complete genomes are of microbes; the term "full genome" is thus sometimes used loosely to mean "greater than 95%". The remainder of this article focuses on nearly complete human genomes.

High-throughput genome sequencing technologies have largely been used as a research tool and are currently being introduced in the clinics.[3][4][5] In the future of personalized medicine, whole genome sequence data will be an important tool to guide therapeutic intervention.[6] The tool of gene sequencing at SNP level is also used to pinpoint functional variants from association studies and improve the knowledge available to researchers interested in evolutionary biology, and hence may lay the foundation for predicting disease susceptibility and drug response.

The shift from manual DNA sequencing methods such as Maxam-Gilbert sequencing and Sanger sequencing in the 1970s and 1980s to more rapid, automated sequencing methods in the 1990s played a crucial role in giving scientists the ability to sequence whole genomes.[8]Haemophilus influenzae, a commensal bacterium which resides in the human respiratory tract was the first organism to have its entire genome sequenced (Figure 2.1). The entire genome of this bacterium was published in 1995.[9] The genomes of H. influenzae, other Bacteria, and some Archaea were the first to be sequenced - largely due to their small genome size. H. influenzae has a genome of 1,830,140 base pairs of DNA.[9] In contrast, eukaryotes, both unicellular and multicellular such as Amoeba dubia and humans (Homo sapiens) respectively, have much larger genomes (see C-value paradox).[10]Amoeba dubia has a genome of 700 billion nucleotide pairs spread across thousands of chromosomes.[11] Humans contain fewer nucleotide pairs (about 3.2 billion in each germ cell - note the exact size of the human genome is still being revised) than A. dubia however their genome size far outweighs the genome size of individual bacteria.[12]

The first bacterial and archaeal genomes, including that of H. influenzae, were sequenced by Shotgun sequencing.[9] In 1996, the first eukaryotic genome ( the yeast Saccharomyces cerevisiae) was sequenced. S. cerevisiae, a model organism in biology has a genome of only around 12 million nucleotide pairs,[13] and was the first unicellular eukaryote to have its whole genome sequenced. The first multicellular eukaryote, and animal, to have its whole genome sequenced was the nematode worm: Caenorhabditis elegans in 1998.[14] Eukaryotic genomes are sequenced by several methods including Shotgun sequencing of short DNA fragments and sequencing of larger DNA clones from DNA libraries (see library (biology)) such as Bacterial artificial chromosomes (BACs) and Yeast artificial chromosomes (YACs).[15]

In 1999, the entire DNA sequence of human chromosome 22, the shortest human autosome, was published.[16] By the year 2000, the second animal and second invertebrate (yet first insect) genome was sequenced - that of the fruit fly Drosophila melanogaster - a popular choice of model organism in experimental research.[17] The first plant genome - that of the model organism Arabidopsis thaliana - was also fully sequenced by 2000.[18] By 2001, a draft of the entire human genome sequence was published.[19] The genome of the laboratory mouse Mus musculus was completed in 2002.[20]

In 2004, the Human Genome Project published the human genome.[21]

Currently, thousands of genomes have been sequenced.

Almost any biological sample containing a full copy of the DNAeven a very small amount of DNA or ancient DNAcan provide the genetic material necessary for full genome sequencing. Such samples may include saliva, epithelial cells, bone marrow, hair (as long as the hair contains a hair follicle), seeds, plant leaves, or anything else that has DNA-containing cells.

The genome sequence of a single cell selected from a mixed population of cells can be determined using techniques of single cell genome sequencing. This has important advantages in environmental microbiology in cases where a single cell of a particular microorganism species can be isolated from a mixed population by microscopy on the basis of its morphological or other distinguishing characteristics. In such cases the normally necessary steps of isolation and growth of the organism in culture may be omitted, thus allowing the sequencing of a much greater spectrum of organism genomes.[22]

Single cell genome sequencing is being tested as a method of preimplantation genetic diagnosis, wherein a cell from the embryo created by in vitro fertilization is taken and analyzed before embryo transfer into the uterus.[23] After implantation, cell-free fetal DNA can be taken by simple venipuncture from the mother and used for whole genome sequencing of the fetus.[24]

Sequencing of nearly an entire human genome was first accomplished in 2000 partly through the use of shotgun sequencing technology. While full genome shotgun sequencing for small (40007000 base pair) genomes was already in use in 1979,[25] broader application benefited from pairwise end sequencing, known colloquially as double-barrel shotgun sequencing. As sequencing projects began to take on longer and more complicated genomes, multiple groups began to realize that useful information could be obtained by sequencing both ends of a fragment of DNA. Although sequencing both ends of the same fragment and keeping track of the paired data was more cumbersome than sequencing a single end of two distinct fragments, the knowledge that the two sequences were oriented in opposite directions and were about the length of a fragment apart from each other was valuable in reconstructing the sequence of the original target fragment.

The first published description of the use of paired ends was in 1990 as part of the sequencing of the human HPRT locus,[26] although the use of paired ends was limited to closing gaps after the application of a traditional shotgun sequencing approach. The first theoretical description of a pure pairwise end sequencing strategy, assuming fragments of constant length, was in 1991.[27] In 1995 the innovation of using fragments of varying sizes was introduced,[28] and demonstrated that a pure pairwise end-sequencing strategy would be possible on large targets. The strategy was subsequently adopted by The Institute for Genomic Research (TIGR) to sequence the entire genome of the bacterium Haemophilus influenzae in 1995,[29] and then by Celera Genomics to sequence the entire fruit fly genome in 2000,[30] and subsequently the entire human genome. Applied Biosystems, now called Life Technologies, manufactured the automated capillary sequencers utilized by both Celera Genomics and The Human Genome Project.

While capillary sequencing was the first approach to successfully sequence a nearly full human genome, it is still too expensive and takes too long for commercial purposes. Since 2005 capillary sequencing has been progressively displaced by next-generation sequencing technologies such as Illumina dye sequencing, pyrosequencing, and SMRT sequencing.[31] All of these technologies continue to employ the basic shotgun strategy, namely, parallelization and template generation via genome fragmentation.

Other technologies are emerging, including nanopore technology. Though nanopore sequencing technology is still being refined, its portability and potential capability of generating long reads are of relevance to whole-genome sequencing applications.[32]

In principle, full genome sequencing can provide raw data on all six billion nucleotides in an individual's DNA. However, it does not provide an analysis of what that information means or how it might be utilized in various clinical applications, such as in medicine to help prevent disease. Work toward that goal is continuously moving forward.

Because sequencing generates a lot of data (for example, there are approximately six billion base pairs in each human diploid genome), its output is stored electronically and requires a large amount of computing power and storage capacity. Full genome sequencing would have been nearly impossible before the advent of the microprocessor, computers, and the Information Age.

A 2015 study[33] done at Children's Mercy Hospital in Kansas City detailed the use of full genome sequencing including full analysis. The process took a record breaking 26 hours[34] and was done using Illumina HiSeq machines, the Edico Genome Dragen Processor, and several custom designed software packages. Most of this acceleration was achieved using the newly developed Dragen Processor which brought the analysis time down from 15 hours to 40 minutes.

A number of public and private companies are competing to develop a full genome sequencing platform that is commercially robust for both research and clinical use,[35] including Illumina,[36]Knome,[37]Sequenom,[38]454 Life Sciences,[39] Pacific Biosciences,[40]Complete Genomics,[41]Helicos Biosciences,[42]GE Global Research (General Electric), Affymetrix, IBM, Intelligent Bio-Systems,[43] Life Technologies and Oxford Nanopore Technologies.[44] These companies are heavily financed and backed by venture capitalists, hedge funds, and investment banks.[45][46]

In October 2006, the X Prize Foundation, working in collaboration with the J. Craig Venter Science Foundation, established the Archon X Prize for Genomics,[47] intending to award US$10million to "the first Team that can build a device and use it to sequence 100 human genomes within 10 days or less, with an accuracy of no more than one error in every 1,000,000 bases sequenced, with sequences accurately covering at least 98% of the genome, and at a recurring cost of no more than $1,000per genome".[48] An error rate of 1in 1,000,000bases, out of a total of approximately six billion bases in the human diploid genome, would mean about 6,000errors per genome. The error rates required for widespread clinical use, such as predictive medicine[49] is currently set by over 1,400 clinical single gene sequencing tests[50] (for example, errors in BRCA1 gene for breast cancer risk analysis).

The Archon X Prize for Genomics was cancelled in 2013, before its official start date.[51][52]

In 2007, Applied Biosystems started selling a new type of sequencer called SOLiD System.[53] The technology allowed users to sequence 60 gigabases per run.[54]

In June 2009, Illumina announced that they were launching their own Personal Full Genome Sequencing Service at a depth of 30 for $48,000 per genome.[55][56]

In August 2009, the founder of Helicos Biosciences, Stephen Quake, stated that using the company's Single Molecule Sequencer he sequenced his own full genome for less than $50,000.[57]

In November 2009, Complete Genomics published a peer-reviewed paper in Science demonstrating its ability to sequence a complete human genome for $1,700.[58][59]

In May 2011, Illumina lowered its Full Genome Sequencing service to $5,000 per human genome, or $4,000 if ordering 50 or more.[60] Helicos Biosciences, Pacific Biosciences, Complete Genomics, Illumina, Sequenom, ION Torrent Systems, Halcyon Molecular, NABsys, IBM, and GE Global appear to all be going head to head in the race to commercialize full genome sequencing.[31][61]

A series of publications in 2012 showed the utility of SMRT sequencing from Pacific Biosciences in generating full genome sequences with de novo assembly.[62]

With sequencing costs declining, a number of companies began claiming that their equipment would soon achieve the $1,000 genome: these companies included Life Technologies in January 2012,[63]Oxford Nanopore Technologies in February 2012[64] and Illumina in February 2014.[65][66]

However, as of 2015, the NHGRI estimates the cost of obtaining a whole-genome sequence at around $1,500.[67]

Full genome sequencing provides information on a genome that is orders of magnitude larger than that provided by the previous leader in genotyping technology, DNA arrays. For humans, DNA arrays currently provide genotypic information on up to one million genetic variants,[68][69][70] while full genome sequencing will provide information on all six billion bases in the human genome, or 3,000times more data. Because of this, full genome sequencing is considered a disruptive innovation to the DNA array markets as the accuracy of both range from 99.98% to 99.999% (in non-repetitive DNA regions) and their consumables cost of $5000 per 6 billion base pairs is competitive (for some applications) with DNA arrays ($500per 1 million basepairs).[39]Agilent, another established DNA array manufacturer, is working on targeted (selective region) genome sequencing technologies.[71] It is thought that Affymetrix, the pioneer of array technology in the 1990s, has fallen behind due to significant corporate and stock turbulence and is currently not working on any known full genome sequencing approach.[72][73][74] It is unknown what will happen to the DNA array market once full genome sequencing becomes commercially widespread, especially as companies and laboratories providing this disruptive technology start to realize economies of scale. It is postulated, however, that this new technology may significantly diminish the total market size for arrays and any other sequencing technology once it becomes commonplace for individuals and newborns to have their full genomes sequenced.[75]

Whole genome sequencing has established the mutation frequency for whole human genomes. The mutation frequency in the whole genome between generations for humans (parent to child) is about 70 new mutations per generation.[76][77] An even lower level of variation was found comparing whole genome sequencing in blood cells for a pair of monozygotic (identical twins) 100-year-old centenarians.[78] Only 8 somatic differences were found, though somatic variation occurring in less than 20% of blood cells would be undetected.

In the specifically protein coding regions of the human genome, it is estimated that there are about 0.35 mutations that would change the protein sequence between parent/child generations (less than one mutated protein per generation).[79]

In cancer, mutation frequencies are much higher, due to genome instability. This frequency can further depend on patient age, exposure to DNA damaging agents (such as UV-irradiation or components of tobacco smoke) and the activity/inactivity of DNA repair mechanisms.[80] Furthermore, mutation frequency can vary between cancer types: in germline cells, mutation rates occur at approximately 0.023 mutations per megabase, but this number is much higher in breast cancer (1.18-1.66 mutations per Mb), in lung cancer (17.7) or in melanomas (~33).[81]

Inexpensive, time-efficient full genome sequencing will be a major accomplishment not only for the field of genomics, but for the entire human civilization because, for the first time, individuals will be able to have their entire genome sequenced. Utilizing this information, it is speculated that health care professionals, such as physicians and genetic counselors, will eventually be able to use genomic information to predict what diseases a person may get in the future and attempt to either minimize the impact of that disease or avoid it altogether through the implementation of personalized, preventive medicine. Full genome sequencing will allow health care professionals to analyze the entire human genome of an individual and therefore detect all disease-related genetic variants, regardless of the genetic variant's prevalence or frequency. This will enable the rapidly emerging medical fields of predictive medicine and personalized medicine and will mark a significant leap forward for the clinical genetic revolution. Full genome sequencing is clearly of great importance for research into the basis of genetic disease and has shown significant benefit to a subset of individuals with rare disease in the clinical setting.[82][83][84][85] Illumina's CEO, Jay Flatley, stated in February 2009 that "A complete DNA read-out for every newborn will be technically feasible and affordable in less than five years, promising a revolution in healthcare" and that "by 2019 it will have become routine to map infants' genes when they are born".[86] This potential use of genome sequencing is highly controversial, as it runs counter to established ethical norms for predictive genetic testing of asymptomatic minors that have been well established in the fields of medical genetics and genetic counseling.[87][88][89][90] The traditional guidelines for genetic testing have been developed over the course of several decades since it first became possible to test for genetic markers associated with disease, prior to the advent of cost-effective, comprehensive genetic screening. It is established that norms, such as in the sciences and the field of genetics, are subject to change and evolve over time.[91][92] It is unknown whether traditional norms practiced in medical genetics today will be altered by new technological advancements such as full genome sequencing.

In March 2010, researchers from the Medical College of Wisconsin announced the first successful use of whole-genome sequencing to inform the treatment of a patient.[93][94]

Currently available newborn screening for childhood diseases allows detection of rare disorders that can be prevented or better treated by early detection and intervention. Specific genetic tests are also available to determine an etiology when a child's symptoms appear to have a genetic basis. Full genome sequencing, in addition has the potential to reveal a large amount of information (such as carrier status for autosomal recessive disorders, genetic risk factors for complex adult-onset diseases, and other predictive medical and non-medical information) that is currently not completely understood, may not be clinically useful to the child during childhood, and may not necessarily be wanted by the individual upon reaching adulthood.[95] In addition to predicting disease risk in childhood, genetic testing may have other benefits (such as discovery of non-paternity) but may also have potential downsides (genetic discrimination, loss of anonymity, and psychological impacts).[96] Many publications regarding ethical guidelines for predictive genetic testing of asymptomatic minors may therefore have more to do with protecting minors and preserving the individual's privacy and autonomy to know or not to know their genetic information, than with the technology that makes the tests themselves possible.[97]

Due to recent cost reductions (see above) whole genome sequencing has become a realistic application in DNA diagnostics. In 2013, the 3Gb-TEST consortium obtained funding from the European Union to prepare the health care system for these innovations in DNA diagnostics.[98][99]Quality assessment schemes, Health technology assessment and guidelines have to be in place. The 3Gb-TEST consortium has identified the analysis and interpretation of sequence data as the most complicated step in the diagnostic process.[100] At the Consortium meeting in Athens in September 2014, the Consortium coined the word genotranslation for this crucial step. This step leads to a so-called genoreport. Guidelines are needed to determine the required content of these reports.

The majority of ethicists insist that the privacy of individuals undergoing genetic testing must be protected under all circumstances.[101] Data obtained from whole genome sequencing can not only reveal much information about the individual who is the source of DNA, but it can also reveal much probabilistic information about the DNA sequence of close genetic relatives.[102] Furthermore, the data obtained from whole genome sequencing can also reveal much useful predictive information about the relatives present and future health risks.[103] This raises important questions about what obligations, if any, are owed to the family members of the individuals who are undergoing genetic testing. In the Western/European society, tested individuals are usually encouraged to share important information on the genetic diagnosis with their close relatives since the importance of the genetic diagnosis for offspring and other close relatives is usually one of the reasons for seeking a genetic testing in the first place.[101] Nevertheless, a major ethical dilemma can develop when the patients refuse to share information on a diagnosis that is made for serious genetic disorder that is highly preventable and where there is a high risk to relatives carrying the same disease mutation.[102] Under such circumstances, the clinician may suspect that the relatives would rather know of the diagnosis and hence the clinician can face a conflict of interest with respect to patient-doctor confidentiality.[102]

Another major privacy concern is the scientific need to put information on patient's genotypes and phenotypes into the public scientific databases such as the locus specific databases.[102] Although only anonymous patient data are submitted to the locus specific databases, patients might still be identifiable by their relatives in the case of finding a rare disease or a rare missense mutation.[102]

The first nearly complete human genomes sequenced were two caucasians in 2007 (J. Craig Venter at 7.5-fold coverage,[104][105][106] and James Watson at 7.4-fold).[107][108][109] This was followed in 2008 by sequencing of an anonymous Han Chinese man (at 36-fold),[110] a Yoruban man from Nigeria (at 30-fold),[111] and a female caucasian Leukemia patient (at 33 and 14-fold coverage for tumor and normal tissues).[112]Steve Jobs was among the first 20 people to have their whole genome sequenced, reportedly for the cost of $100,000.[113] As of June 2012[update], there are 69 nearly complete human genomes publicly available.[114]Commercialization of full genome sequencing is in an early stage and growing rapidly.

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List of countries by life expectancy – Wikipedia

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This is a collection of lists of countries by average life expectancy at birth.

Life expectancy equals the average number of years a person born in a given country is expected to live if mortality rates at each age were to remain steady in the future. The life expectancy is shown separately for males and females, as well as a combined figure. Several non-sovereign entities are also included in this list too.

The figures reflect the quality of healthcare in the countries listed as well as other factors including ongoing wars, obesity, and HIV infections.[citation needed]

Worldwide, the average life expectancy at birth was 71.0 years (68 years and 6 months for males and 73 years and 6 months for females) over the period 20102013 according to United Nations World Population Prospects 2012 Revision,[3] or 70.7 years (68.2 years for males and 73.2 years for females) for 2009 according to The World Factbook.[4] According to the World Health Organization (WHO), women on average live longer than men in all countries, with the exception of Tonga.

The countries with the lowest overall life expectancies per the WHO are Sierra Leone, the Central African Republic, the Democratic Republic of the Congo, Guinea-Bissau, Lesotho, Somalia, Swaziland, Angola, Chad, Mali, Burundi, Cameroon, and Mozambique. Of those countries, only Lesotho, Swaziland, and Mozambique in 2011 were suffering from an HIV prevalence rate of greater than 10 percent in the 1549 age group.[5]

Comparing life expectancies from birth across countries can be problematic. There are differing definitions of live birth vs stillbirth even among more developed countries and less developed countries often have poor reporting.[6]

2015 data[7] published in May 2016.[8]

HALE: Health-adjusted life expectancy[9]

On July 2015, the Population Division of the United Nations Department of Economic and Social Affairs (UN DESA), released World Population Prospects, The 2015 Revision.[3] The following table shows the life expectancy at birth for the period 2010 to 2015.

over 80

77.5-80.0

75.0-77.5

72.5-75.0

70.0-72.5

67.5-70.0

65.0-67.5

60-65

55-60

50-55

45-50

under 45

not available

The Global Burden of Disease 2010 study published updated figures in 2012,[10] including recalculations of life expectancies[11] which differ substantially in places from the UN estimates for 2010 (reasons for this are discussed in the freely available appendix to the paper, pages 2527, currently not available). Although no estimate is given for the sexes combined, for the first time life expectancy estimates have included uncertainty intervals.

>80

>77.5

>75

>72.5

>70

>67.5

>65

>60

>55

>50

>45

>40

<40

The US CIA published the following life expectancy data in its annual world factbook 2012.[1]

Figures are from the CIA World Factbook 2009[1] and from the 2010 revision of the United Nations World Population Prospects report, for 20052010,[3] (data viewable at http://esa.un.org/wpp/Sorting-Tables/tab-sorting_mortality.htm, with equivalent spreadsheets here, here, and here).

Only countries/territories with a population of 100,000 or more in 2010 are included in the United Nations list. WHO database 2013 http://www.who.int/gho/publications/world_health_statistics/EN_WHS2013_Full.pdf

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Ron Paul: The real meaning of populism – CNN.com

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The 2016 presidential race, in photos

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Louisa Hill, 3, walks onto a stage in Hanover, New Hampshire, as Clinton speaks on July 3, 2015.

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Bush is seen on a camera at the Iowa State Fair on August 14, 2015.

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Cruz speaks during the annual banquet of the Iowa Faith & Freedom Coalition on September 19, 2015.

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Clinton, right, appears on an episode of "Saturday Night Live" opposite Kate McKinnon, who has been playing Clinton during the campaign, on October 3, 2015.

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Trump is flanked by impersonators Taran Killam, left, and Darrell Hammond during his "Saturday Night Live" monologue on November 7, 2015.

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Sanders sits in an Atlanta cafe with rapper Killer Mike on November 23, 2015. The rapper introduced Sanders at a campaign event later that day.

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Hidayah Martinez Jaka wears an American flag hijab as Democratic presidential candidate Martin O'Malley speaks at a mosque in Sterling, Virginia, on December 11, 2015.

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A supporter reacts as Trump signs her poster during a campaign rally in Lowell, Massachusetts, on January 4, 2016.

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A protester is removed by security personnel during a Trump campaign event in Rock Hill, South Carolina, on January 8, 2016.

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While visiting the Civil Rights Institute in Birmingham, Alabama, on January 18, 2016, Sanders touches the actual jail bars that the Rev. Martin Luther King Jr. was behind when he wrote his "Letter from Birmingham Jail" in 1963.

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A giant Trump poster is illuminated outside a home in Des Moines, Iowa, on January 28, 2016.

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Republican presidential candidate Rick Santorum, second from right, drinks a beer at a pub in Waukee, Iowa, on January 28, 2016. The former U.S. senator from Pennsylvania also ran in 2012.

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A woman in a Princess Leia costume makes a "Star Wars"-themed plea for Sanders during a campaign rally in Cedar Rapids, Iowa, on January 30, 2016.

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Sanders speaks during a campaign event in Des Moines, Iowa, on January 31, 2016.

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Clinton plays goalie during a campaign stop at an indoor-soccer center in Las Vegas on February 13, 2016. After her loss in New Hampshire, Clinton rebounded to win the Nevada primary on February 20.

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Cruz speaks from a truck bed at a rally in Pahrump, Nevada, on February 21, 2016.

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Bernie Sanders is joined by his wife, Jane, at a rally in Burlington, Vermont, on March 1, 2016. Sanders won his state's primary on Super Tuesday, but he lost to Clinton in seven of the other 10 states.

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Ohio Gov. John Kasich, one of the Republican presidential candidates, poses with a Sanders impersonator at the end of a town-hall meeting in Palatine, Illinois, on March 9, 2016.

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Kasich celebrates his Ohio primary victory on March 15, 2016. It was the only win of his campaign.

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Cruz laughs at a poster while speaking a town-hall event in Madison, Wisconsin, on March 30, 2016.

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Kasich has lunch at a deli during a campaign stop in New York on April 7, 2016.

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Clinton shakes hands during a campaign event in Wilmington, Delaware, on April 25, 2016.

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