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Alzheimer's diseaseNo end to dementia
Ten years ago people talked confidently of stopping Alzheimer’s disease in its tracks. Now, they realise they have no idea how to do that Jun 17th 2010

DRUG companies are notoriously secretive. The clock starts running on a patent when it is filed, so the longer something can be kept under wraps before that happens, the better for the bottom line. You know something is up, then, when a group of these firms announce they are banding together to share the results of abandoned drug trials. And on June 11th several big companies did just that. They publicised the profiles of 4,000 patients from 11 trials so that they could learn from each other’s failures. An act of selflessness, perhaps, but also one of desperation.
Alzheimer’s disease is one of those things that policymakers would rather hide from. It is, perhaps, the classic illness of old age. Physical frailty is expected, and can be coped with. Mental frailty is much scarier for the sufferer and more demanding for those who have to look after him. It is expensive, too. Alzheimer’s is estimated to cost America alone some $170 billion a year. And it is getting commoner as average lifespans increase. The number of people suffering from the disease is expected to triple by 2050. Effective treatments would thus be embraced with enthusiasm by sufferers and society alike. The right Alzheimer’s drug could earn a drugmaker a lot of money. The incentives are there. But the science has still failed to deliver.
At the turn of the century, Alzheimer’s research seemed promising. A flurry of drugs which treated symptoms of the disorder had just hit the market and researchers were setting out confidently on a deeper investigation of its causes. Understanding those, they felt sure, would result in a cure. It still might, but the truth is that the hoped-for understanding has not come. As a consequence, a long list of would-be cures have failed in late-stage clinical trials, at enormous cost to the companies producing them. The latest of these, Dimebon, made by Pfizer, was abandoned as recently as March, after $725m had been spent on research and development.

Beta testing
The problem of what causes Alzheimer’s is profound. The physical manifestations of the disease that Alois Alzheimer noticed in 1906 are sticky plaques of one type of protein, now known as beta-amyloid, and nerve-cell-engulfing tangles of a second type, called tau protein. Since 1991 the smart money has been on the hypothesis that the disease is caused by the plaques, and that the tangles are mere consequence. For the past two decades, therefore, most attention has been given to developing drugs that will remove amyloid plaques from an affected brain. Five drugs that do this are on the market, but they only delay the onset of dementia. Once their effectiveness has run its course, memory loss and cognitive decline progress unimpeded, and sometimes even accelerate.
Partly as a consequence of this, the plaque theory is waning. Most researchers still believe beta-amyloid is the culprit, but the idea that free-floating protein molecules, rather than the proteins in the plaques, are to blame is gaining ground. This idea is supported by a study published in April in the Annals of Neurology, which showed that mice without plaques, but with floating beta-amyloid, were just as weakened by the disease as mice with both. If that is true in people, too, many more drugs now in clinical trials may prove to be ineffective.
Another fundamental problem is that, whatever is causing the damage, treatment is starting too late. By the time someone presents behavioural symptoms, such as forgetfulness, his brain is already in a significant state of disrepair. Even a “cure” is unlikely to restore lost function. A biochemical marker that indicates the progress of the disease would thus help identify those for whom early action would be advisable, and might help to distinguish people with Alzheimer’s from those with the less hostile forms of forgetfulness that tend to come with old age. Such a marker would also benefit the organisers of clinical trials. They would be able to see more easily whether a drug was working.
To this end, the Alzheimer’s Disease Neuroimaging Initiative (ADNI), established by America’s National Institutes of Health (NIH) in 2004, is measuring the levels of certain proteins in the cerebrospinal fluid of people who may have Alzheimer’s or may go on to develop it. Though the project still has a long way to go, it has already helped develop a test to diagnose the early stages of the disease.
ADNI’s anagram DIAN, the Dominantly Inherited Alzheimer Network, based at Washington University in St Louis, is taking another approach to the biomarker question. Its researchers are studying families with a genetic mutation that triggers the early onset of Alzheimer’s. That terrible knowledge means it is possible to predict which members of a family are destined to get the disease, and compare their biochemistry with that of relatives who do not have the mutation.
It is hard pounding, however, and—as the drug companies’ confession suggests—it is the “R” rather than the “D” of research and development that needs to be emphasised at the moment. A bad time, then, to be cutting back on “R”. That tripling of future sufferers is going to be expensive. Yet Alzheimer’s research, on which the NIH spent $643m in 2006, is to receive only $480m in 2011. It has not been singled out for these cuts. They are part of a general belt-tightening at the agency. But in this as in everything, you get what you pay for. And that might, in the future, be an awful lot of witless, wandering elderly.

Rose@MayUID：2797727

Surgical technologyAn in-depth operation
3D: coming soon, to an operating theatre near you Jun 17th 2010 | Guildford
Do Na’vi actually have gall bladders?

IN “AVATAR”, a film that has enjoyed a certain modest success at the box office recently, 3D technology brought blue-skinned extraterrestrials to life. On June 10th, a similar innovation helped improve life on Earth when Iain Jourdan, a surgeon at the Royal Surrey County Hospital, in Guildford, England, donned polarising glasses to perform the first-ever laparoscopic surgery assisted by three-dimensional imaging.
The procedure he performed, a routine gall-bladder removal, is typically done by incising a slit in the patient’s navel, through which a tiny camera is inserted. Guided by the resulting video feed, the surgeon wields long-handled tools to excavate the gall bladder from its neighbouring organs before removing it though the slit. Until now, however, that video has been in two dimensions. Anyone who has tried threading a needle with one eye shut will understand that this is not ideal.

Past attempts to design a 3D display for use in the operating theatre have not worked. One prototype, a stereoscopic helmet worn by the surgeon, left users seasick after only a few minutes. The new system, manufactured by Solid-Look, a firm based in New York, abandons such missteps in favour of technology originally developed for the entertainment industry: 3D glasses and a specially modified television screen.
During the surgery, a camera sends back two live video feeds taken from slightly different angles, as it surveys the abdominal cavity from within. The signals are polarised in opposite directions, and the resulting images displayed as alternating rows of pixels on a high-definition television screen. The polarising lenses of the glasses filter these images, meaning each eye sees only one of them. The brain then adds them together as if they were natural, to create the impression of depth, as well as width and height.
The resulting vista of receding cavities and organic bulges allows for more accurate cutting and stitching. The first gall bladder removed by Mr Jourdan using the new system was extracted in 30 minutes, less than the normal average.
3D thus looks as though it could be poised for a dramatic future. And with the laparoscopic-device market valued at more than $5 billion a year, the new technology could soon be a medical, as well as cinematic, blockbuster.

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A special report on debt
Repent at leisure
Borrowing has been the answer to all economic troubles in the past 25 years. Now debt itself has become the problem, says Philip Coggan

Jun 24th 2010

MAN is born free but is everywhere in debt. In the rich world, getting hold of your first credit card is a rite of passage far more important for your daily life than casting your first vote. Buying your first home normally requires taking on a debt several times the size of your annual income. And even if you shun the temptation of borrowing to indulge yourself, you are still saddled with your portion of the national debt.

Throughout the 1980s and 1990s a rise in debt levels accompanied what economists called the “great moderation”, when growth was steady and unemployment and inflation remained low. No longer did Western banks have to raise rates to halt consumer booms. By the early 2000s a vast international scheme of vendor financing had been created. China and the oil exporters amassed current-account surpluses and then lent the money back to the developed world so it could keep buying their goods.

Those who cautioned against rising debt levels were dismissed as doom-mongers; after all, asset prices were rising even faster, so balance-sheets looked healthy. And with the economy buoyant, debtors could afford to meet their interest payments without defaulting. In short, it paid to borrow and it paid to lend.
In this special report

    * » Repent at leisure «
    * Paradise foreclosed
    * The morning after
    * Betting the balance-sheet
    * A better bust?
    * The unkindest cuts
    * Judging the judges
    * In a hole
    * Offer to readers
    * Sources and acknowledgments

Like alcohol, a debt boom tends to induce euphoria. Traders and investors saw the asset-price rises it brought with it as proof of their brilliance; central banks and governments thought that rising markets and higher tax revenues attested to the soundness of their policies.

The answer to all problems seemed to be more debt. Depressed? Use your credit card for a shopping spree “because you’re worth it”. Want to get rich quick? Work for a private-equity or hedge-fund firm, using borrowed money to enhance returns. Looking for faster growth for your company? Borrow money and make an acquisition. And if the economy is in recession, let the government go into deficit to bolster spending. When the European Union countries met in May to deal with the Greek crisis, they proposed a

AdelineShenUID：2630498

A special report on gambling    Shuffle up and deal
    The internet is radically changing the business of gambling. Now policy must catch up, argues Jon Fasman          Jul 8th 2010         
         
PINPOINTING a precise moment when the world changes is never easy, even in retrospect. Yet it is possible to say with relative confidence that the world of gambling was changed dramatically by events around a green felt table at Binion’s Horseshoe in Las Vegas on May 23rd 2003, the final day of that year’s World Series of Poker (WSOP). The hand immediately preceding the final table—the last nine of the tournament’s 839 competitors who would play for $2.5m—pitted Phil Ivey, one of the sharpest and most ruthless players of his time, against Chris Moneymaker, an unknown 27-year-old accountant from Nashville. The newcomer eliminated Mr Ivey thanks to a lucky draw on the last card dealt. Mr Ivey, a stone-faced old-school player, declined to shake his vanquisher’s hand. Mr Moneymaker went on to win the tournament.
His victory created what came to be called “the Moneymaker effect”: interest in poker soared. Suddenly spending time playing a game on a computer looked like a road to riches. And those riches seemed attainable. The stars in poker, unlike those in professional sport, look very much like the spectators; they just happen to be more successful. In the years since Mr Moneymaker’s victory, the tournament has variously been won by a patent lawyer, a Hollywood agent and a 21-year-old professional poker player.
It is not just professional poker that has changed out of all recognition in the past decade but all forms of gambling worldwide. The reason has been simple: for the first time anyone who wants to gamble and has an internet connection can do so. The desire has been there for much of recorded history. An excavation of a bronze-age city in south-eastern Iran turned up a pair of dice dating back nearly 5,000 years. Islam forbids gambling, but the Bible mentions casting lots or using fortune to determine an outcome. Card-playing for money has often been depicted in art (see detail above of Georges de la Tour’s “The Cheat with the Ace of Diamonds”, circa 1635-40).
            In this special report

• » Shuffle up and deal «
• The risk instinct
• At war with luck
• Bet on the bot
• Log on, ante up
• Lengthening odds
• Cutting off the arms
• When the chips are down
• The dragon's gambling den
• Come, all ye gullible
• Sure thing
• Sources and acknowledgments
• Offer to readers

   
  Gambling’s widespread and enduring appeal comes as much from the hope of imposing order on the fundamental randomness of the world as from the expectation of economic gain (though that certainly has its charms). Blaming a bad result on an offended spirit or a good result on divine favour is far more comforting than accepting the cold indifference of probability.
But there is a darker side to gambling with which ancient civilisations were also well acquainted. The Rig Veda, a collection of Hindu religious hymns more than 3,000 years old, contains a section known as the Gambler’s Hymn which laments: “Without any fault of hers I have driven my devoted wife away because of a die exceeding by one [an unsuccessful bet]. My mother-in-law hates me; my wife pushes me away. In his defeat the gambler finds none to pity him. No one has use for a gambler, like an aged horse put up for sale.”
As the newly single poet above had just discovered, the numbers make most forms of gambling a mug’s game. The odds of winning the jackpot in America’s richest lottery, Mega Millions, is one in 176m. EuroMillions, available to players in nine western European countries, offers slightly better odds: one in 76m. Roulette players, on average, will hit their number once in 36 or 37 attempts. Poker players’ chances of being dealt a royal flush are much the same as being struck by lightning.

A majority sport


Yet hope never dies. In 2007 nearly half of America’s population and over two-thirds of Britain’s bet on something or other. Hundreds of millions of lottery tickets are sold every week. The global gambling market is estimated to be worth around $335 billion a year (see chart 1). Last year Las Vegas alone raked in gambling revenues of $10.4 billion and Macau $14.7 billion.
For Las Vegas, that represents a decline in revenue from 2008. By contrast, revenues from online gambling continue to rise. H2 Gambling Capital, a consultancy that monitors the global gambling market, estimates online gambling revenues in 2009 at around $26 billion (see chart 2). The world’s gambling centres are no longer just Vegas, Macau and Monaco; they now also include Alderney, Gibraltar, Antigua and Malta, whose favourable tax systems make them irresistible homes for internet-based companies.


Thanks to these companies the old restrictions have started to crumble. Government prohibition of online gambling has worked about as well as prohibition of other online content, which is to say it is observed mainly in the breach. America remains the world’s biggest single online gambling market by far, despite the passage in 2006 of the Unlawful Internet Gaming Enforcement Act (UIGEA)—a provision tacked onto a port-security bill that prohibits the transfer of funds from a financial institution to an online gambling site. After the ban some established sites closed down their American operations, but others filled the void. Americans are gambling roughly the same amount online as they did in 2006.
The move online threatens some traditional forms of gambling, such as betting on horses, but appears to benefit others, such as slot machines and lotteries. And bricks-and-mortar expansion still continues. The latest addition to the Las Vegas Strip, CityCenter, opened last December. Covering 76 acres (31 hectares) and costing around $8.5 billion, it is the largest privately funded construction project in American history. Thirty-three American states have casinos (many of them operated by around 200 Native American tribes), as do more than 20 countries across Europe. The Las Vegas Sands Corporation, which owns the Venetian casinos in Las Vegas and Macau, opened Marina Bay Sands in Singapore in April. Sheldon Adelson, Sands’s chief executive, believes that Asia can easily accommodate “five to ten Las Vegases”.
In the past ten years gambling has changed more than in the previous 70. The internet has forced existing businesses to adapt, opened up new opportunities and fundamentally altered the political, economic, corporate and moral climate in which these businesses operate. This special report will trace those changes through the main forms of gambling, which sadly will mean neglecting strong but local passions such as greyhound racing, bingo, jai alai and cricket fights. It will begin with Mr Moneymaker’s game.

AdelineShenUID：2630498

A special report on Egypt    The long wait
    After three decades of economic progress but political paralysis, change is in the air, says Max Rodenbeck          Jul 15th 2010         
         
TRAVELLING into Cairo, Egypt’s monster-sized but curiously intimate capital, it is hard to tell if these are the best of times or the worst. Visitors who have long known the city are in two minds. Egyptian expatriates returning home are liable to cringe at the worse-than-ever traffic, the ever-louder noise, the fervid religiosity, and what they often bemoan as a new aggressiveness that spoils their nostalgia for a sweeter, cheerier Egypt. But tourists who came here, say, 20 years ago, tend to delight in the sleeker look of the place, the surprisingly efficient and still friendly service, the far better quality and variety of goods in the markets, and the fact that some taxis now actually have functioning meters.
Both impressions are right. The new World Bank-funded, Turkish-built terminal at Cairo International airport is as blandly functional as Cincinnati’s or Stockholm’s. Gone are the sweaty officials and greasy baggage handlers of yore, the taxi touts and shoving crowds. A businessman arriving here may be whisked in an Egyptian-built car to the cigar bar at one of Cairo’s dozens of swish hotels—perhaps one at City Stars, a commercial complex on the scale and in the style of Las Vegas. Or perhaps to another fancy hotel in one of the burgeoning gated exurbs in the desert, surrounded by the lavishly watered greenery of a designer golf course. There, the talk will be of beach houses and yachts on the Red Sea, of hot stocks on the Cairo exchange, and of Egypt’s delightfully low-cost labour.
A less lucky traveller, however, might instead see these things as most Egyptians do: in the giant backlit billboards that clutter Cairo’s roadsides and rooftops, vividly flaunting the unattainable. The consumer paradise they display, with perfect hair, light-skinned children and men in pinstripe suits, stands in stark contrast to the harried, shuffling crowds below. Such sights will probably be accompanied by an earful of complaint from the driver stuck in a jam: about corrupt traffic cops and the absurd impossibility of feeding and schooling the kids on $150 a month, but above all about politics, the staple of all Middle Eastern conversationalists.
            In this special report

• Sources and acknowledgments
• » The long wait «
• America's lieutenant
• The best man always wins
• A favoured spot
• Long-sighted
• A slow learning curve
• No paradise
• Saving faith
• After Mubarak
• Offer to readers

   
   Political talk in Egypt has always been acidly cynical, but now a new bitterness has crept in. This has not been prompted by any change from above, since little has really changed in Egyptian politics since President Hosni Mubarak came to office 29 years ago. The sour mood is informed instead by the contrast between rising aspirations and enduring hardships; by a growing sense of alienation from the state; and by the unease of anticipation as the end of an era inevitably looms ever closer.
It is not surprising that Egyptians should feel rather like driftwood on the Nile, accelerating towards one of the great river’s cataracts. Their current pharaoh is 82 years old, visibly ailing, and has no anointed successor. Most of his people have known no other leader. The vast majority have grown so inured to having no say in the course of events that the reflex is to float patiently rather than try to paddle. Parliamentary elections are scheduled for November this year and presidential ones for September next. As usual, few citizens are likely to take part. They will watch from the sidelines and accept the preordained results with grim humour.

Losing patience
Nevertheless, the expectation of a seismic shift is almost tangible in the air, and not just because of Mr Mubarak’s health. Egyptians may be renowned for being politically passive, but the rising generation is very different from previous ones. It is better educated, highly urbanised, far more exposed to the outside world and much less patient. Increasingly, the whole structure of Egypt’s state, with its cumbersome constitution designed to disguise one-man rule, its creaky centralised administration, its venal, brutal and unaccountable security forces and its failure to deliver such social goods as decent schools, health care or civic rights, looks out of kilter with what its people want.


For some time Egyptian commentators have been noting resemblances between now and the years before Egypt’s previous seismic shift. That happened in 1952, when a group of army officers rolled their tanks up to King Farouk’s palaces and tossed him out. The coup was wildly popular at the time. It had followed a period of drift and growing tension, marked by strikes, assassinations, riots and intrigues between Communists, Muslim Brothers and the king. Egypt was thriving economically, but the spoils flowed mostly to a cosmopolitan elite that was out of tune with the street. It had a functioning democracy, but ever-squabbling politicians seemed unable to get things done. To general chagrin they could not shake off the lingering influence of Britain, whose soldiers refused to budge from the Suez Canal where they had been encamped since 1882.
The officers’ coup replaced this genteel but dysfunctional constitutional monarchy with one-party rule, fronted by a strongman and backed by secret police, with the tanks idling nearby. Republican Egypt became a model for other Arab dictatorships and forced wrenching changes at home. Its promises of free health and education, land reform and jobs in state factories and offices did lift millions out of misery to mere poverty. The ideology of pan-Arabism trumpeted by the coup leader, Gamal Abdel Nasser, gave Egyptians a place of pride in the world, even if his boldness brought ruinous wars in Yemen and against Israel.
Six decades and four presidents on, the revolutionary regime has metamorphosed into one that encourages private business and allows for some pluralism. Yet it looks to many Egyptians like a waning dynasty—the 45th in the long line of houses that have ruled the world’s most enduring nation since 3000BC. Its promises are largely in tatters. Schools and hospitals are indeed free to enter, but they are grim, bare, crowded places where getting learning or treatment requires cash that many still do not have. The lower middle class of army officers and bureaucrats who rose in the revolution have joined the gentry they were supposed to have ousted, adopted their haughty ways and now share Egypt’s spoils with them. The poor still queue for government-subsidised bread and must scrimp and save to buy a pair of shoes.
The government’s plan to perpetuate itself in office, via the traditional electoral rigmarole, is likely to go ahead. Predictions of change in Egypt have almost always proved wrong; generally it bumbles along much as usual. This time may just be different. The country now faces three main possibilities. It could go the way of Russia and be ruled by a new strongman from within the system. It might, just possibly, go the way of Iran, and see that system swept away in anger. Or it could go the way of Turkey, and evolve into something less brittle and happier for all concerned