Thursday, September 27, 2007
Children of men - the movie
I watched Children of Men on DVD last night. I was luke warm about the book - the first part was moving and interesting, but the plot resolution in the second half was lame and unbelievable. The film is indescribably bad. The Mexican director, Alfonso Cuaron, has been lauded for his approach, but he has produced a routine thriller with poor continuity. The characters retain only their names. The poignancy of a world without children has been completely lost; the religious sensitivity of PD James has been trampled on; and teh director has highjacked the story to make a left-wing statement about illegal immigrants and Guantanamo Bay. If you want to watch this film, I would advise not switching on the sub-titles. That way about half the profanities will go unheard.
Tuesday, September 25, 2007
2007 and all that
I was reminded yesterday that I hadn't blogged for a week; was I still alive? Alive, certainly, but busy. I have been painting the back of the house. We have one of those black and white, mock-Tudor houses. It is around 100 years old with the original wooden window frames. When I addressed the problem it was clear that the paint was stronger than the wood. It was necessary to do some remedial work before I could get the paint-brush out. These old houses are very impressive but they do require maintenance.
At the weekend my son visited us. David is an engineer who works for AP Racing. The company made its name by designing and manufacturing the clutch for the Ford Cosworth engine, which for many years was the basis of most car racing. He is an expert on brakes, and designed the brakes on many of the fastest cars on the planet. His role this year is to be the AP representative at the races. He has just returned from Salt Lake City where he covered some sort of racing event, but he had a free weekend to come and visit his ageing parents.
We took a walk on the beach on Sunday morning. The weather was balmy with a south west breeze and very few people around. Seven miles of sand in a long curve with cliffs behind. This is the time to best appreciate Bournemouth. The visitors have gone home, but it is still warm enough to walk in your shirtsleeves. Now the residents can enjoy the scenery without the smell of suntan oil and hot dogs. The cliffs here are covered with vegetation. I picked out wild roses, Michaelmas daisies and evening primrose, but there were many other species that I didn't recognize.
We have been talking about moving from Bournemouth, though it would be hard to leave. This is one of the most pleasant sections of the English coastline. However, we haven't walked on the beach since February and we could achieve that frequency if we lived in Birmingham.
In Bournemouth this week are the Labor Party for their annual Conference. Gordon Brown gave his first Conference speech as Prime Minister. There is talk of an early election so that he can have his own mandate, instead of inheriting Tony Blair's In fact there is no need. He has two and a half years before he need to call an election. This is a parliamentary, rather than Presidential, form of government.
Last night I watched a television program about the making of the film, Billy Eliot. Most of my readers will know that this is the story set against the miner's strike of 1984 of a young working class, miner's son who wants to become a ballet dancer. In the film they used the local ex-miners as extras. They were happy to play the striking miners, but no-one wanted to play the policemen who broke the strike. Not living in such an area I find it hard to appreciate the vehemence with which these communities hates (and still hate) Mrs Thatcher.
My take on British history since the second world war is that 1945 saw an irrevocable change. Workers were no longer content to be led by the 'Officer class'. They had seen for themselves that it was the sergeants who were the real leaders. Sure there were real leaders like Churchill and Montgomery who knew how to fight, but the young men from public schools who were the subalterns and junior officers were in the main no more fit to lead, and often far less so, than the NCOs who were their erstwhile mates. The Attlee government nationalized everything. Post war Britain was all but bankrupt, its industry had been bombed and much of its housing stock destroyed. Although it still had its bright young men and its Nobel prizes (the structure of DNA was discovered in Cambridge in 1953), its industry was old fashioned, the class structure was still ossifying society, and capital was in short supply. The Attlee government was stuffed with effete intellectuals and tough Union leaders. They were not up to the task. On an island built of coal and surrounded by fish they had contrived by 1947 to produce a shortage of both - as Sir Anthony Eden adroitly remarked. Their vision outran their competence.
Churchill's government of the fifties had the advantage of time passing since the war. Economic recovery had begun. But Britain had to come to terms with its new place in the world. As America's largest ally in Korea, it felt itself still to be a great power, but when the conspiracy with France and Israel to attack Suez and retake the Canal failed because America opposed it, the new Prime Minister, Macmillan, had to readjust to the new world. Britain acted quickly to divest itself of its Empire. India had gone in 1947, the White Dominions could stand on their own feet, and the rest was a burden rather than a benefit. Empire became Commonwealth, but Africa had little share in the common wealth. Following the Indian example the African colonies each produced their own Nehru, and endowed with schools, a civil service and the Church of England stepped out towards disaster.
Profumo brought down the Conservatives. Despite relative success of Macmillan's government - they were building 300,000 houses a year, there were new roads and railways, new schools and hospitals were constructed and the exploitation of the African had ended - they were still members of a different class. Profumo emphasized that. While the rest of us were working out butts off for the country, here was a member of the government consorting with call-girls, living it up at a country house and probably spilling secrets as he shared a mistress with a Russian spy. It was too much for Macmillan who fell ill, and when the Tories replaced him with the 14th Earl of Home, our suspicions were confirmed. We wanted one of us to lead us, not one of them.
The sixties were all about young people. The Beatles, the Prague Spring, Paris 68, Jack Kennedy, Viet Nam: Harold Wilson exploited the situation well. He was an Oxford intellectual who pretended to be working class. He affected a broad Yorkshire accent, smoked a pipe and entertained visitors to 10 Downing Street with beer and sandwiches rather than fine wines and French haute cuisine. He declined to send troops to Viet Nam, pursued Keynesian economics, let inflation rip, allowed the Trades Unions to dominate politics, spent taxpayers money on propping up ailing industries and presided over decline. It was like that line of Wilfred Owen's: "A slow drawing down of blinds."
The Tories gave us a Wilson clone in Edward Heath. A one-nation Tory, he pursued much the same economic policies as Wilson. Heath was a bachelor who loved classical music and yachting. His great ambition was to enter the Common Market as it was then known. Everyone envied the German economic miracle and wanted the same for themselves. The French wanted to keep it for themselves. Heath bought his way in. I guess his ambition was colored by the War. He had been a major in the Tank Corps and had been decorated. He saw the European Economic Community as the sure way to end war in Europe.
My view on Europe is different. Cynically, I regard it as a plot by the French to enforce the same sort of reparations on Germany as they did after the first world war. In trying to avoid another Hitler arising they locked Germany into a social arrangement by which German profits would featherbed French farmers while keeping Germany as a good neighbor. Naturally De Gaulle didn't want the British to have a share of the cake. The terms that Heath agreed to were such that the British ended up paying the French too (for having the cheek to save French bacon). Of course America was the real funder through the Marshall plan.
But it wasn't Europe that brought him down, it was the economy. The British economy had been growing at a rather slower rate than the German one, but it had been growing. Despite large numbers of immigrants from Jamaica and the Indian sub-continent there was a shortage of labor and the Unions exploited this. The main industries - coal, steel, automobile, telecommunications, shipbuilding, the docks and the railways had all been nationalized so the Unions had the ability to hold the country to ransom. The Arabs had shown how to do it by raising the oil price. Without fuel the wheels don't turn.
The coal miners went on strike. To save fuel Heath introduced a three day week. Electricity was cut off at regular intervals to spread the pain around. We were lucky; we lived next door to a hospital which was spared. Heath called a snap election on the issue of who rules - the Unions or the Government? But people were sick of the privation and voted Labor.
Wilson was back and his Industry Minister Eric Varley settled with the miners by giving them a 30% pay rise, but Wilson immediately recognized that the Unions had to be tamed. He instructed Barbara Castle to introduce legislation to curb them. "In Place of Strife" was hated by the Unions who mobilized their MPs to fight it. Their chief supporter was Jim Callaghan, a man who has the signal honor of holding the four great offices of state - Prime Minister, Foreign Secretary, Chancellor of the Exchequer and Home Secretary, and failing in every one of them. In a Cabinet revolt he defeated Barbara Castle. The Unions were unfettered, and in a surprise decision, perhaps because he recognized the beginnings of dementia, Wilson resigned.
Callaghan succeeded him and led the country into chaos. By 1979 strikes ruled. The economy had collapsed. The dead remained unburied, garbage was uncollected in the streets and rats had started invading people's house. Callaghan clung on until the last moment.
Then came Mrs Thatcher. It was not easy. To control inflation Geoffrey Howe produced a severely deflationary budget. It was not popular. The mood of the country was against her. Then the Argentinians invaded the Falklands. It was a Godsend. She mounted a task force with an 8000 mile logistic tail that retook the islands. It was difficult; we lost a lot of men, but it proved that low as we had sunk, we were still superior to some jumped up banana republic run by a bunch of Nazis whose heroes cheat at football.
Thatcher was re-elected and made plans to tackle the miners. It was a re-run of 1973-4. Scargill wanted to emulate Gormley, but he was a much nastier piece of work. Thatcher had prepared well. Coal stocks were at an all-time high and many of the power stations were gas-fired. She weathered the storm. Despite violent demonstrations, bullying and bitter enmity between working men, the miners were defeated and the Unions were broken. The great state monopolies were broken up and privatized. Anti-Union legislation reduced their powers. A stronger Mrs Thatcher even renegotiated the terms of EU membership and won a rebate on the punitive cost we were paying the French. She won a third term.
She fell over two issues. She would not pay for recombinant factor VIII for hemophiliacs and she replaced domestic rates (which had become unworkable) by a flat rate tax. This was dubbed the Poll tax by Labor bringing back memories of Wat Tyler. The Tories felt she had outlived her usefulness and brought in John Major who was supposed to lose in 1992. He won. Tempted by Europe to start to merge currencies, his first move was met by a run on the pound. The speculators won and Major was diminished. Not only was he now a lame duck, but he faced Tony Blair, a different kind of Labor leader.
Blair adopted Thatcher's economic policies, resisted the Unions, and to a degree kept the Chancellor's hands off interest rates. The economy boomed. His foreign policy involved interfering in the internal runnings of rogue states. This was successful in Bosnia, Sierra Leone and Kosovo, but Iraq became a millstone around his neck. His successor, Gordon Brown, is benefiting from not being Tony Blair, and despite being equally to blame for Iraq carries none of the fall-out from it. He has the reputation of a successful finance minister, but so far even the first run on a British bank for 147 years has not harmed him. Can it last?
He appeared in Bournemouth this week in sober suit against a blue (Tory) background and mentioned 'Britain' or 'British' 71 times in his speech. As a Scottish MP he is vulnerable to Scottish nationalism. He is also facing difficulties over Europe. His manifesto promised a referendum on the new European constitution. That was kicked into the long grass by the French and the Dutch, but has been resurrected, only slightly altered as a Treaty. He no longer wants a referendum (which would be lost), but if he calls an election it will become a referendum on Europe. Whatever the polls say, he might lose.
At the weekend my son visited us. David is an engineer who works for AP Racing. The company made its name by designing and manufacturing the clutch for the Ford Cosworth engine, which for many years was the basis of most car racing. He is an expert on brakes, and designed the brakes on many of the fastest cars on the planet. His role this year is to be the AP representative at the races. He has just returned from Salt Lake City where he covered some sort of racing event, but he had a free weekend to come and visit his ageing parents.
We took a walk on the beach on Sunday morning. The weather was balmy with a south west breeze and very few people around. Seven miles of sand in a long curve with cliffs behind. This is the time to best appreciate Bournemouth. The visitors have gone home, but it is still warm enough to walk in your shirtsleeves. Now the residents can enjoy the scenery without the smell of suntan oil and hot dogs. The cliffs here are covered with vegetation. I picked out wild roses, Michaelmas daisies and evening primrose, but there were many other species that I didn't recognize.
We have been talking about moving from Bournemouth, though it would be hard to leave. This is one of the most pleasant sections of the English coastline. However, we haven't walked on the beach since February and we could achieve that frequency if we lived in Birmingham.
In Bournemouth this week are the Labor Party for their annual Conference. Gordon Brown gave his first Conference speech as Prime Minister. There is talk of an early election so that he can have his own mandate, instead of inheriting Tony Blair's In fact there is no need. He has two and a half years before he need to call an election. This is a parliamentary, rather than Presidential, form of government.
Last night I watched a television program about the making of the film, Billy Eliot. Most of my readers will know that this is the story set against the miner's strike of 1984 of a young working class, miner's son who wants to become a ballet dancer. In the film they used the local ex-miners as extras. They were happy to play the striking miners, but no-one wanted to play the policemen who broke the strike. Not living in such an area I find it hard to appreciate the vehemence with which these communities hates (and still hate) Mrs Thatcher.
My take on British history since the second world war is that 1945 saw an irrevocable change. Workers were no longer content to be led by the 'Officer class'. They had seen for themselves that it was the sergeants who were the real leaders. Sure there were real leaders like Churchill and Montgomery who knew how to fight, but the young men from public schools who were the subalterns and junior officers were in the main no more fit to lead, and often far less so, than the NCOs who were their erstwhile mates. The Attlee government nationalized everything. Post war Britain was all but bankrupt, its industry had been bombed and much of its housing stock destroyed. Although it still had its bright young men and its Nobel prizes (the structure of DNA was discovered in Cambridge in 1953), its industry was old fashioned, the class structure was still ossifying society, and capital was in short supply. The Attlee government was stuffed with effete intellectuals and tough Union leaders. They were not up to the task. On an island built of coal and surrounded by fish they had contrived by 1947 to produce a shortage of both - as Sir Anthony Eden adroitly remarked. Their vision outran their competence.
Churchill's government of the fifties had the advantage of time passing since the war. Economic recovery had begun. But Britain had to come to terms with its new place in the world. As America's largest ally in Korea, it felt itself still to be a great power, but when the conspiracy with France and Israel to attack Suez and retake the Canal failed because America opposed it, the new Prime Minister, Macmillan, had to readjust to the new world. Britain acted quickly to divest itself of its Empire. India had gone in 1947, the White Dominions could stand on their own feet, and the rest was a burden rather than a benefit. Empire became Commonwealth, but Africa had little share in the common wealth. Following the Indian example the African colonies each produced their own Nehru, and endowed with schools, a civil service and the Church of England stepped out towards disaster.
Profumo brought down the Conservatives. Despite relative success of Macmillan's government - they were building 300,000 houses a year, there were new roads and railways, new schools and hospitals were constructed and the exploitation of the African had ended - they were still members of a different class. Profumo emphasized that. While the rest of us were working out butts off for the country, here was a member of the government consorting with call-girls, living it up at a country house and probably spilling secrets as he shared a mistress with a Russian spy. It was too much for Macmillan who fell ill, and when the Tories replaced him with the 14th Earl of Home, our suspicions were confirmed. We wanted one of us to lead us, not one of them.
The sixties were all about young people. The Beatles, the Prague Spring, Paris 68, Jack Kennedy, Viet Nam: Harold Wilson exploited the situation well. He was an Oxford intellectual who pretended to be working class. He affected a broad Yorkshire accent, smoked a pipe and entertained visitors to 10 Downing Street with beer and sandwiches rather than fine wines and French haute cuisine. He declined to send troops to Viet Nam, pursued Keynesian economics, let inflation rip, allowed the Trades Unions to dominate politics, spent taxpayers money on propping up ailing industries and presided over decline. It was like that line of Wilfred Owen's: "A slow drawing down of blinds."
The Tories gave us a Wilson clone in Edward Heath. A one-nation Tory, he pursued much the same economic policies as Wilson. Heath was a bachelor who loved classical music and yachting. His great ambition was to enter the Common Market as it was then known. Everyone envied the German economic miracle and wanted the same for themselves. The French wanted to keep it for themselves. Heath bought his way in. I guess his ambition was colored by the War. He had been a major in the Tank Corps and had been decorated. He saw the European Economic Community as the sure way to end war in Europe.
My view on Europe is different. Cynically, I regard it as a plot by the French to enforce the same sort of reparations on Germany as they did after the first world war. In trying to avoid another Hitler arising they locked Germany into a social arrangement by which German profits would featherbed French farmers while keeping Germany as a good neighbor. Naturally De Gaulle didn't want the British to have a share of the cake. The terms that Heath agreed to were such that the British ended up paying the French too (for having the cheek to save French bacon). Of course America was the real funder through the Marshall plan.
But it wasn't Europe that brought him down, it was the economy. The British economy had been growing at a rather slower rate than the German one, but it had been growing. Despite large numbers of immigrants from Jamaica and the Indian sub-continent there was a shortage of labor and the Unions exploited this. The main industries - coal, steel, automobile, telecommunications, shipbuilding, the docks and the railways had all been nationalized so the Unions had the ability to hold the country to ransom. The Arabs had shown how to do it by raising the oil price. Without fuel the wheels don't turn.
The coal miners went on strike. To save fuel Heath introduced a three day week. Electricity was cut off at regular intervals to spread the pain around. We were lucky; we lived next door to a hospital which was spared. Heath called a snap election on the issue of who rules - the Unions or the Government? But people were sick of the privation and voted Labor.
Wilson was back and his Industry Minister Eric Varley settled with the miners by giving them a 30% pay rise, but Wilson immediately recognized that the Unions had to be tamed. He instructed Barbara Castle to introduce legislation to curb them. "In Place of Strife" was hated by the Unions who mobilized their MPs to fight it. Their chief supporter was Jim Callaghan, a man who has the signal honor of holding the four great offices of state - Prime Minister, Foreign Secretary, Chancellor of the Exchequer and Home Secretary, and failing in every one of them. In a Cabinet revolt he defeated Barbara Castle. The Unions were unfettered, and in a surprise decision, perhaps because he recognized the beginnings of dementia, Wilson resigned.
Callaghan succeeded him and led the country into chaos. By 1979 strikes ruled. The economy had collapsed. The dead remained unburied, garbage was uncollected in the streets and rats had started invading people's house. Callaghan clung on until the last moment.
Then came Mrs Thatcher. It was not easy. To control inflation Geoffrey Howe produced a severely deflationary budget. It was not popular. The mood of the country was against her. Then the Argentinians invaded the Falklands. It was a Godsend. She mounted a task force with an 8000 mile logistic tail that retook the islands. It was difficult; we lost a lot of men, but it proved that low as we had sunk, we were still superior to some jumped up banana republic run by a bunch of Nazis whose heroes cheat at football.
Thatcher was re-elected and made plans to tackle the miners. It was a re-run of 1973-4. Scargill wanted to emulate Gormley, but he was a much nastier piece of work. Thatcher had prepared well. Coal stocks were at an all-time high and many of the power stations were gas-fired. She weathered the storm. Despite violent demonstrations, bullying and bitter enmity between working men, the miners were defeated and the Unions were broken. The great state monopolies were broken up and privatized. Anti-Union legislation reduced their powers. A stronger Mrs Thatcher even renegotiated the terms of EU membership and won a rebate on the punitive cost we were paying the French. She won a third term.
She fell over two issues. She would not pay for recombinant factor VIII for hemophiliacs and she replaced domestic rates (which had become unworkable) by a flat rate tax. This was dubbed the Poll tax by Labor bringing back memories of Wat Tyler. The Tories felt she had outlived her usefulness and brought in John Major who was supposed to lose in 1992. He won. Tempted by Europe to start to merge currencies, his first move was met by a run on the pound. The speculators won and Major was diminished. Not only was he now a lame duck, but he faced Tony Blair, a different kind of Labor leader.
Blair adopted Thatcher's economic policies, resisted the Unions, and to a degree kept the Chancellor's hands off interest rates. The economy boomed. His foreign policy involved interfering in the internal runnings of rogue states. This was successful in Bosnia, Sierra Leone and Kosovo, but Iraq became a millstone around his neck. His successor, Gordon Brown, is benefiting from not being Tony Blair, and despite being equally to blame for Iraq carries none of the fall-out from it. He has the reputation of a successful finance minister, but so far even the first run on a British bank for 147 years has not harmed him. Can it last?
He appeared in Bournemouth this week in sober suit against a blue (Tory) background and mentioned 'Britain' or 'British' 71 times in his speech. As a Scottish MP he is vulnerable to Scottish nationalism. He is also facing difficulties over Europe. His manifesto promised a referendum on the new European constitution. That was kicked into the long grass by the French and the Dutch, but has been resurrected, only slightly altered as a Treaty. He no longer wants a referendum (which would be lost), but if he calls an election it will become a referendum on Europe. Whatever the polls say, he might lose.
Monday, September 17, 2007
Alan Greenspan speaks
Margaret Thatcher appeared frail last week when Gordon Brown welcomed her to 10 Downing Street as an honoured guest. he was only doing her the same courtesy as previous premiers had done. All invite their predecessors in for a look round to see how the place is changing. Nevertheless it caused him some aggro at the Trades Union Congress, where she remains a hated figure.
To my mind the Blessed Margaret did two things for Britain that have cemented her place in history. The first was to dare to mount a military operation 8000 miles away to retake the Falklands. People forget that Britain was in seriously decline before that. In 1979 a strike in the public sector had left the dead unburied and garbage uncollected so that there were rats running rife in the streets. The Argentinian Junta must have thought that Britain was so weak that it wouldn't bother over a couple of rocks in the South Atlantic close to Antarctica where a couple of thousand sheep farmers live. I'm still not sure what motivated Margaret; I was in America at the time and I seriously doubted that Britain had the military strength to mount an operation so far away. I suspect it was when she saw that the Falklands were being forced to drive on the right. Anyway, despite setbacks, the Falklands were retaken by acts if bravery or fortitude. A right wing dictatorship was overthrown.
The other great thing she did was to defeat the miners. A decade earlier a Conservative government had been overthrown by Joe Gormley, the miners' leader, but this time she was ready for them. When Arthur Scargill attempted the same trick and used even more violent tactics than Gormley, he was defeated and the grip of the Labor movement was broken. Britain would no longer be a communist fellow-traveler; the economy was turned around by flexible labor laws and the Labor party would not return to power until Tony Blair reformed it, changing it into a party of the right.
Alan Greenspan, quoted in the Telegraph this morning concurs:
"You [in the UK] haven't even had a taint of a recession for an extremely long period of time – and a goodly part of that is the flexibility that came out of the crush between Scargill and Thatcher," he says.
"That was the defining moment, and to their credit Blair and Brown did not endeavour to unwind it. They recognised that there was something fundamentally good for British labour in having a flexible economy."
To my mind the Blessed Margaret did two things for Britain that have cemented her place in history. The first was to dare to mount a military operation 8000 miles away to retake the Falklands. People forget that Britain was in seriously decline before that. In 1979 a strike in the public sector had left the dead unburied and garbage uncollected so that there were rats running rife in the streets. The Argentinian Junta must have thought that Britain was so weak that it wouldn't bother over a couple of rocks in the South Atlantic close to Antarctica where a couple of thousand sheep farmers live. I'm still not sure what motivated Margaret; I was in America at the time and I seriously doubted that Britain had the military strength to mount an operation so far away. I suspect it was when she saw that the Falklands were being forced to drive on the right. Anyway, despite setbacks, the Falklands were retaken by acts if bravery or fortitude. A right wing dictatorship was overthrown.
The other great thing she did was to defeat the miners. A decade earlier a Conservative government had been overthrown by Joe Gormley, the miners' leader, but this time she was ready for them. When Arthur Scargill attempted the same trick and used even more violent tactics than Gormley, he was defeated and the grip of the Labor movement was broken. Britain would no longer be a communist fellow-traveler; the economy was turned around by flexible labor laws and the Labor party would not return to power until Tony Blair reformed it, changing it into a party of the right.
Alan Greenspan, quoted in the Telegraph this morning concurs:
"You [in the UK] haven't even had a taint of a recession for an extremely long period of time – and a goodly part of that is the flexibility that came out of the crush between Scargill and Thatcher," he says.
"That was the defining moment, and to their credit Blair and Brown did not endeavour to unwind it. They recognised that there was something fundamentally good for British labour in having a flexible economy."
Sunday, September 16, 2007
Chromosomes at IWCLL
In my first report from the IWCLL I want to focus on chromosomes. FISH - fluorescent in-situ hybridization is the mainstay of chromosomal examination in CLL. With this technique florescent probes are used to detect certain DNA sequences in the CLL nucleus. It has the advantage that the cell does not have to divide in order to be examined. and because of this many cells can be examines (typically 200). The disadvantage is that you can only see what you look for - usually deletions at 13q14, 11q23 and 17p13 plus trisomy 12. Sometimes del 6q is also looked for. There were reports at this meeting of the use of other techniques including looking for copy number changes and loss of heterozygosity using high density SNP arrays, and new mitotic agents to induce cell division.
In the SNP array paper from Freiburg, Germany an area at 2p16 that contains came under REL and BCL11A came under suspicion. BCL11A was one of the genes that is differentially expressed in mutated and unmutated patients, identified by the original Rosenwald paper.
Most people cannot get CLL cells to divide properly. A good way of checking whether chromosome banding techniques are successful is to compare the percentage of del 13q14 patients that are detected by banding and FISH. Most people find many more by FISH and by this reckoning only the Haferlach group at Munich and the Oscier group in Bournemouth are any good at chromosome banding in CLL, and both reported their results here. The Munch group largely confirmed the results that had previously been found by FISH, but added the fact that chromosomal translocations occur in about 20% of patients. Most involve either 14q32 or 13q14, and they are usually not balanced - the involve a loss of chromosomal material - effectively they are deletions. They do not have common partners and they do not form fusion genes. They also reported that trisomies of 3, 18 and 19 are seen as well as trisomy 12. Finally, about 16% have complex karyotypes which are usually associated with bad prognosis markers.
The Oscier group reported on karyotyic evolution. this can be detected by demonstrating sub-populations of cells with none, one, two or three abnormalities apparently acquired in a sequential way (eg 10% of cells have normal karyotypes, 27% just del 13q14, 48% of cells del 13q14 plus del 11q23, and the rest del 13q14, del 11q23 and del 17p13). Or they cen be demonstrated by watching for changes on sequential samples taken at interval - this would include someone who had 14% del 13q14 at diagnosis, but 85% del 13q14 four years later. The Oscier group reported on 342 patients. In 103 there was evidence that karyotypic evolution had occurred prior to diagnosis. 314 had a second sample taken after an interval of at least a year. Patients had a median of 4 (range 2-13) samples taken. 189 patients eventually showed evidence of karyotypic evolution (ie 55%). There were specific patterns of evolution. Those with trisomy 12 (which was almost universally a primary event) either acquired a 14q32 translocation (t14;18 or t14;19) or developed further trisomies (of 19, 18 or less commonly 3). Further trisomies only occurred on a background of trisomy 12, and only occurred in those with mutated VH genes.
In patients withdel 13q14 the commonest progression was for the other chromosome to become involved with a similar lesion. These has been some debate as to whether this carries a poor prognosis. Other groups (including the Munich group) have suggested that it might do so although the figures do not reach statistical significance, However, in this series those with the second chromosome involved actually did significantly better than those with only one - possibly because this is a relatively late phenomenon, and the patient has to survive a long time without acquiring a different chromosomal abnormality in order to just have a homozygous deletion at 13q.
The hunt for the gene responsible at 13q14 has been long and apparently fruitless. The missing chromosomal portion was first reported in 1987:
Chromosome abnormalities involving band 13q14 in hematologic malignancies
Margaret Fitchett, Michael J. Griffiths, David G. Oscier, Sharron Johnson and Marina Seabright Cancer Genetics and Cytogenetics Volume 24, Issue 1, January 1987, Pages 143-150.
There have been several attempts to identify the genes on the missing fragment, largely by Dr Oscier's group, but to no avail until the problem attracted the big boys, Carlo Croce and Ricardo Dalla-Favera. They both agreed that there was no gene coding for any tumor-suppressor protein at this site. Croce's wide reading led him to microRNA genes and the discovery that two such genes, miR-16-1/miR-15a were located within the deleted area. miR genes interfere with the expression of messenger RNA, and thus the expression of a target protein. At least one of the targets of these genes is BCL-2, so that if they are missing BCL-2 is over-expressed and, as everyone knows, BCL-2 is over-expressed in CLL. this is thought to at least partly explain the resistance to apoptosis.
The miR genes in CLL are very close to one of the introns for Leu-2, a gene that is not translated into protein. Dalla-Favera decided to investigate what Leu-2 does. He produced evidence that Leu-2 is a long controlling gene. Thus it is not clear whether the effect of the 13q deletion is mediated just through the miR genes or whether the whole Leu-2 gene acts epigenetically to control some important function in B cells and that loss of this function leads to leukemia.
In the SNP array paper from Freiburg, Germany an area at 2p16 that contains came under REL and BCL11A came under suspicion. BCL11A was one of the genes that is differentially expressed in mutated and unmutated patients, identified by the original Rosenwald paper.
Most people cannot get CLL cells to divide properly. A good way of checking whether chromosome banding techniques are successful is to compare the percentage of del 13q14 patients that are detected by banding and FISH. Most people find many more by FISH and by this reckoning only the Haferlach group at Munich and the Oscier group in Bournemouth are any good at chromosome banding in CLL, and both reported their results here. The Munch group largely confirmed the results that had previously been found by FISH, but added the fact that chromosomal translocations occur in about 20% of patients. Most involve either 14q32 or 13q14, and they are usually not balanced - the involve a loss of chromosomal material - effectively they are deletions. They do not have common partners and they do not form fusion genes. They also reported that trisomies of 3, 18 and 19 are seen as well as trisomy 12. Finally, about 16% have complex karyotypes which are usually associated with bad prognosis markers.
The Oscier group reported on karyotyic evolution. this can be detected by demonstrating sub-populations of cells with none, one, two or three abnormalities apparently acquired in a sequential way (eg 10% of cells have normal karyotypes, 27% just del 13q14, 48% of cells del 13q14 plus del 11q23, and the rest del 13q14, del 11q23 and del 17p13). Or they cen be demonstrated by watching for changes on sequential samples taken at interval - this would include someone who had 14% del 13q14 at diagnosis, but 85% del 13q14 four years later. The Oscier group reported on 342 patients. In 103 there was evidence that karyotypic evolution had occurred prior to diagnosis. 314 had a second sample taken after an interval of at least a year. Patients had a median of 4 (range 2-13) samples taken. 189 patients eventually showed evidence of karyotypic evolution (ie 55%). There were specific patterns of evolution. Those with trisomy 12 (which was almost universally a primary event) either acquired a 14q32 translocation (t14;18 or t14;19) or developed further trisomies (of 19, 18 or less commonly 3). Further trisomies only occurred on a background of trisomy 12, and only occurred in those with mutated VH genes.
In patients withdel 13q14 the commonest progression was for the other chromosome to become involved with a similar lesion. These has been some debate as to whether this carries a poor prognosis. Other groups (including the Munich group) have suggested that it might do so although the figures do not reach statistical significance, However, in this series those with the second chromosome involved actually did significantly better than those with only one - possibly because this is a relatively late phenomenon, and the patient has to survive a long time without acquiring a different chromosomal abnormality in order to just have a homozygous deletion at 13q.
The hunt for the gene responsible at 13q14 has been long and apparently fruitless. The missing chromosomal portion was first reported in 1987:
Chromosome abnormalities involving band 13q14 in hematologic malignancies
Margaret Fitchett, Michael J. Griffiths, David G. Oscier, Sharron Johnson and Marina Seabright Cancer Genetics and Cytogenetics Volume 24, Issue 1, January 1987, Pages 143-150.
There have been several attempts to identify the genes on the missing fragment, largely by Dr Oscier's group, but to no avail until the problem attracted the big boys, Carlo Croce and Ricardo Dalla-Favera. They both agreed that there was no gene coding for any tumor-suppressor protein at this site. Croce's wide reading led him to microRNA genes and the discovery that two such genes, miR-16-1/miR-15a were located within the deleted area. miR genes interfere with the expression of messenger RNA, and thus the expression of a target protein. At least one of the targets of these genes is BCL-2, so that if they are missing BCL-2 is over-expressed and, as everyone knows, BCL-2 is over-expressed in CLL. this is thought to at least partly explain the resistance to apoptosis.
The miR genes in CLL are very close to one of the introns for Leu-2, a gene that is not translated into protein. Dalla-Favera decided to investigate what Leu-2 does. He produced evidence that Leu-2 is a long controlling gene. Thus it is not clear whether the effect of the 13q deletion is mediated just through the miR genes or whether the whole Leu-2 gene acts epigenetically to control some important function in B cells and that loss of this function leads to leukemia.
Saturday, September 15, 2007
IWCLL 2007
This week I have been at the IWCLL meeting in London. This meeting began many years ago in Paris and I have been to most of them. We were shown a photograph of the meeting in Barcelona in 1991 where there were 44 delegates. Most of the 44 were at the London meeting, along with over 700 others. It is no longer a workshop. Nevertheless I would suspect that no disease has shown such an increase in interest over the past 20 years as CLL.
I will be blogging about some of the new stuff to come out of the meeting at a later date, but the hot news is about the Binet-Rai Medal which is presented at the meeting. The medal was first given to Kanti Rai and Jaques-Louis Binet for their invention of the CLL scoring systems. The third medal was given to Michael Keating for his work with fludarabine. The fourth and fifth medals were given to Nick Chiorazzi and myself for the discovery of the importance of VH mutations. The sixth medal was given to Daniel Catovsky for his work on the morphology of CLL and the MRC trials. The seventh medal was awarded this year posthumously to David Galton who died earlier this year. David was one of the first physician scientists to work on CLL and established many of the features of the disease and described lymphocyte doubling time as a prognostic factor. His widow and children accepted it on his behalf. The eighth medal went to Carlo Croce for his discovery of the miR genes 15 and 16 at 13q14 in the minimally deleted region and his TCL-1 mouse model of the disease.
I will be blogging about some of the new stuff to come out of the meeting at a later date, but the hot news is about the Binet-Rai Medal which is presented at the meeting. The medal was first given to Kanti Rai and Jaques-Louis Binet for their invention of the CLL scoring systems. The third medal was given to Michael Keating for his work with fludarabine. The fourth and fifth medals were given to Nick Chiorazzi and myself for the discovery of the importance of VH mutations. The sixth medal was given to Daniel Catovsky for his work on the morphology of CLL and the MRC trials. The seventh medal was awarded this year posthumously to David Galton who died earlier this year. David was one of the first physician scientists to work on CLL and established many of the features of the disease and described lymphocyte doubling time as a prognostic factor. His widow and children accepted it on his behalf. The eighth medal went to Carlo Croce for his discovery of the miR genes 15 and 16 at 13q14 in the minimally deleted region and his TCL-1 mouse model of the disease.
Wednesday, September 12, 2007
The discoverer of leukemia
Rudolf Virchow was one of the two men who first described leukemia in 1845 (the other was John Hughes Bennett, an Englishman who was Professor of Medicine in Scotland). Virchow, as well as being the greatest pathologist ever, was also a Public Health Specialist and social reformer, and something of a politician. In this respect he quarreled with Bismark, the German Chancellor. Bismark challenged him to a duel, and being the one who was challenged, Virchow had the choice of weapons. He chose sausages. I came across this fascinating fact and the mind's picture of two hirsute Germans bashing each other with German sausages was funny but undignified. This is how Virchow wanted to fight to the death with a sausage. He proposed that one of the sausages should be injected with a deadly bacterium. Then each would choose a sausage and eat it. One of them would die a horrible death in writhing agony. After all, skill with a pistol or sword should not be the determining factor in an argument. If they could not agree by discussion, why not let chance sort out their disagreement. Bismark withdrew his challenge.
Sunday, September 09, 2007
Mark 13 finally
As we come to the end of Mark chapter 13, how clued up are we about the Second Coming? There seems no doubt that He is coming. Not only does this the earliest gospel teach it quite plainly in this chapter, but the saying 'Maranatha' (Oh Lord, come!) became a greeting in the early church.
We also know that Jesus himself did not know when he would return (v 23). He accepted the restrictions of the human form at His incarnation, one of which is not being able to know the future. There were some things that had to happen first, though. Wars and rumours of wars, earthquakes, false prophets and the total destruction of the Jerusalem Temple. These things would be fulfilled within one generation (v30). And so they were. By AD70 the time was ripe for the Lord's return; everything that was needful had been.
But that was nearly 2000 years ago; how can it be said to be near?
This is a concept that needs to be clearly understood. It doesn't mean the same as soon. It means imminent; it could happen at any time. The idea of soon is in opposition to the idea that no-one knows the time. It means that nothing is preventing it. There is nothing that has to happen first. Like a seabird skimming over the surface of the water, at any moment it could dip below the surface and take a fish. It is always close, but no-one knows when it will dive.
How do we know he hasn't already come?
Because it will make a real splash when He does come v24-26. As Paul says it will happen with "a loud command, with the voice of the Archangel and the trumpet call of God." (I Thess 4 16) It will not be a hole in the corner affair.
What is the take home message?
We ought to be ready now. Are you thinking that you would like to be a Christian but not yet; you are too busy enjoying yourself? Don't delay, there may not be a 'later'. Are you a Christian but living a worldly life? Why risk all for those things that will perish? Money will be no use to you in Heaven. There are no pockets in a shroud. Even if the Second Coming is after your death, you don't know how many days you have left. Forgive me if this offends you but this Tuesday is 9/11. I imagine that the thousands who died that day were not expecting it. Were they ready? Would you be?
Jesus tells several parables about the unprepared. "If he comes suddenly, do not him find you sleeping. What I say to you, I say to everyone: Watch!"
We also know that Jesus himself did not know when he would return (v 23). He accepted the restrictions of the human form at His incarnation, one of which is not being able to know the future. There were some things that had to happen first, though. Wars and rumours of wars, earthquakes, false prophets and the total destruction of the Jerusalem Temple. These things would be fulfilled within one generation (v30). And so they were. By AD70 the time was ripe for the Lord's return; everything that was needful had been.
But that was nearly 2000 years ago; how can it be said to be near?
This is a concept that needs to be clearly understood. It doesn't mean the same as soon. It means imminent; it could happen at any time. The idea of soon is in opposition to the idea that no-one knows the time. It means that nothing is preventing it. There is nothing that has to happen first. Like a seabird skimming over the surface of the water, at any moment it could dip below the surface and take a fish. It is always close, but no-one knows when it will dive.
How do we know he hasn't already come?
Because it will make a real splash when He does come v24-26. As Paul says it will happen with "a loud command, with the voice of the Archangel and the trumpet call of God." (I Thess 4 16) It will not be a hole in the corner affair.
What is the take home message?
We ought to be ready now. Are you thinking that you would like to be a Christian but not yet; you are too busy enjoying yourself? Don't delay, there may not be a 'later'. Are you a Christian but living a worldly life? Why risk all for those things that will perish? Money will be no use to you in Heaven. There are no pockets in a shroud. Even if the Second Coming is after your death, you don't know how many days you have left. Forgive me if this offends you but this Tuesday is 9/11. I imagine that the thousands who died that day were not expecting it. Were they ready? Would you be?
Jesus tells several parables about the unprepared. "If he comes suddenly, do not him find you sleeping. What I say to you, I say to everyone: Watch!"
War films flagging
'Flags of our Fathers' is a remarkable film. Since the 1960s we have accepted the message that war is horrible and one wonders what more there is to say on that theme. Before then we had seen war movies as keeping your chin up as our economies recovered from WWII. "Cheer up," they seemed to say, "your sacrifice was worth it."
With films like 'The Damn Busters', 'In Which We Serve', 'Reach for the Sky', 'First of the Few', 'The Colditz Story', 'the Battle of Britain', 'Odette', 'Carve her Name with Pride', and 'The Way Ahead', Jack hawkins, John Mills and Dickie Attenborough represented the common man whose steadfastness and courage carried the day. 'The Great Escape' and 'Where Eagles 'Dare turned the war into a Boy's Own adventure. Viet Nam soured any attempt to make war worthwhile. Lately 'Schindler's List' re-exposed us to the harrowing horror of the Nazi's and 'Saving Private Ryan' to the futility of the trying to order events in wartime.
'Flags of our Fathers' exposes the cynicism of politicians and the exploitation of soldiers. It might have been culled from Rudyard Kipling:
We aren't no thin red 'eroes, nor we aren't no blackguards too,
But single men in barricks, most remarkable like you;
An' if sometimes our conduck isn't all your fancy paints,
Why single men in barricks don't grow into plaster saints;
For it's Tommy this, an' Tommy that, an' "Chuck 'im out, the brute!"
But it's "Saviour of 'is country" when the guns begin to shoot;
Obviously, the story of the photograph of the American Flag being raise on Mt Suribachi which inspired the Washington war Memorial will have more significance for Americans than for me, and the story of Ira Hayes (then played by Tony Curtis) has been told before, but as a foreigner I can still get the irony. This is not an anti-war film, but it disparages the notion of heroes. It was necessary to take Iwo Jima. It was necessary to exploit the victory in order to fund the continuation of the war. But men laying down their lives for the country is a fiction. They died unexpectedly, but when they thought about it they died for their buddies.
With films like 'The Damn Busters', 'In Which We Serve', 'Reach for the Sky', 'First of the Few', 'The Colditz Story', 'the Battle of Britain', 'Odette', 'Carve her Name with Pride', and 'The Way Ahead', Jack hawkins, John Mills and Dickie Attenborough represented the common man whose steadfastness and courage carried the day. 'The Great Escape' and 'Where Eagles 'Dare turned the war into a Boy's Own adventure. Viet Nam soured any attempt to make war worthwhile. Lately 'Schindler's List' re-exposed us to the harrowing horror of the Nazi's and 'Saving Private Ryan' to the futility of the trying to order events in wartime.
'Flags of our Fathers' exposes the cynicism of politicians and the exploitation of soldiers. It might have been culled from Rudyard Kipling:
We aren't no thin red 'eroes, nor we aren't no blackguards too,
But single men in barricks, most remarkable like you;
An' if sometimes our conduck isn't all your fancy paints,
Why single men in barricks don't grow into plaster saints;
For it's Tommy this, an' Tommy that, an' "Chuck 'im out, the brute!"
But it's "Saviour of 'is country" when the guns begin to shoot;
Obviously, the story of the photograph of the American Flag being raise on Mt Suribachi which inspired the Washington war Memorial will have more significance for Americans than for me, and the story of Ira Hayes (then played by Tony Curtis) has been told before, but as a foreigner I can still get the irony. This is not an anti-war film, but it disparages the notion of heroes. It was necessary to take Iwo Jima. It was necessary to exploit the victory in order to fund the continuation of the war. But men laying down their lives for the country is a fiction. They died unexpectedly, but when they thought about it they died for their buddies.
Hugh and C(a)ry
Notting Hill I enjoy watching, Four Weddings even more so; About a Boy was good and I really liked Love Actually, but I am afraid that Music and Lyrics with Drew Barrymore is another Mickey Blue Eyes where the Hugh Grant charm doesn't work.
Hugh is often compared to Cary. He is after all an Englishman who went to Hollywood er... called Grant. I am afraid that the comparison does not flatter Hugh. Sure Cary often played himself, but it is hard to believe that an older Hugh will be able to carry a film like North by North West or even Charade.
Hugh is often compared to Cary. He is after all an Englishman who went to Hollywood er... called Grant. I am afraid that the comparison does not flatter Hugh. Sure Cary often played himself, but it is hard to believe that an older Hugh will be able to carry a film like North by North West or even Charade.
Amazing Grace
The actors in this film were unaware of the story of William Wilberforce and even of John Newton. One wonders what is taught in schools today. No wonder people like Dawkins gets away with his claim that religion brings only misery and strife.
The Clapham Sect were a group of remarkable evangelical Anglicans who effected more social change in Nineteenth Century England than any other group - and since at that time England was the only world superpower, the influence was worldwide. Apart from the abolition of the slave trade, whose 200th anniversary this film and this year celebrates, their work led eventually to the emancipation of slaves, a land back in Africa for slaves who wanted to return (Sierra Leone), prison reform, free education and the establishment pf nursing (Florence Nightingale was the granddaughter of one of their members). Their zeal, perseverance, energy and philanthropy changed the world.
What about the movie? The young principals performed well, but were acted off the park by the two seniors, Albert Finney and Michael Gambon. The film was cheaply produced, without special effects and rather 'stagey'. This was the time of the American and French revolutions; we were given no sense of how close England came to suffering the same. We saw the shackles but no slaves. The TV series 'Roots' from many years ago showed us what life was like on the triangular passage; it could only be parsimony that deprived us of a similar visual shock.
I was looking forward to this film but I was disappointed in the result. The British parliament was portrayed as a unicameral affair with Lords and Commons taking part in the same debate. With such an economy with veracity, I didn't know how much of the story I could believe.
The Clapham Sect were a group of remarkable evangelical Anglicans who effected more social change in Nineteenth Century England than any other group - and since at that time England was the only world superpower, the influence was worldwide. Apart from the abolition of the slave trade, whose 200th anniversary this film and this year celebrates, their work led eventually to the emancipation of slaves, a land back in Africa for slaves who wanted to return (Sierra Leone), prison reform, free education and the establishment pf nursing (Florence Nightingale was the granddaughter of one of their members). Their zeal, perseverance, energy and philanthropy changed the world.
What about the movie? The young principals performed well, but were acted off the park by the two seniors, Albert Finney and Michael Gambon. The film was cheaply produced, without special effects and rather 'stagey'. This was the time of the American and French revolutions; we were given no sense of how close England came to suffering the same. We saw the shackles but no slaves. The TV series 'Roots' from many years ago showed us what life was like on the triangular passage; it could only be parsimony that deprived us of a similar visual shock.
I was looking forward to this film but I was disappointed in the result. The British parliament was portrayed as a unicameral affair with Lords and Commons taking part in the same debate. With such an economy with veracity, I didn't know how much of the story I could believe.
Tenderness of Wolves
If you haven't read 'The Tenderness of Wolves', the remarkable first novel by Stef Penney, I strongly recommend that you do. Set as it is in Canada of 1867, it is not immediately the sort of book I go for, and you might find it a trifle slow as it establishes its characters and its place, but persevere and it will reward you perseverance.
In essence it is a detective story, but there is no detective or even a policeman in sight. Mysteries pile up: a murdered man, a lost boy, lost girls, a lost husband, a missing wife, lost firs, a cryptic message, a lost language. The Canadian wilderness is the setting. The settlers are largely Scotch with a smattering of Frenchies. The native Americans have been exploited and ... 'enslaved' is too strong a word, but subjugated certainly. Women are exalted, then owned, then beaten. Boys are groomed, then bullied, then expected to mature - and if they fail they are thrown to the wolves. But in this story wolves hardly feature despite the title. They act as a symbol of the wild, but as we are repeatedly told, they seldom attack humans.
Stef Penney grew up in Edinburgh and studied at Bristol University (my old alma mater) before studying film and TV at the excellent College of Art here in Bournemouth. She was picked up by Carlton Television's New Writers scheme and has written and directed two films. She has never been to Canada and, like Karl Marx before her, did all her research in the British Library. (Why should that surprise us? Had Isaac Asimov ever been to outer space?) She has at least one anachronism: the town of Kitchener was named after the General; in 1867 it was called Berlin.
Mostly things resolve themselves, but with so many plot lines and over 50 characters there are some loose ends. What did happen to Amy Seton? Why was Jammet killed? What was Mrs Ross's first name? (Look away now if you don't want to see the spoilers) The answer to the last is Lucy as can be worked out from pages 165 and 170 and indeed from the final page. Jammet was killed because to prevent him taking what others covered and Amy Seton is surely the subject of another book, just as Mrs Ross's prequel is already the subject of a screenplay.
In essence it is a detective story, but there is no detective or even a policeman in sight. Mysteries pile up: a murdered man, a lost boy, lost girls, a lost husband, a missing wife, lost firs, a cryptic message, a lost language. The Canadian wilderness is the setting. The settlers are largely Scotch with a smattering of Frenchies. The native Americans have been exploited and ... 'enslaved' is too strong a word, but subjugated certainly. Women are exalted, then owned, then beaten. Boys are groomed, then bullied, then expected to mature - and if they fail they are thrown to the wolves. But in this story wolves hardly feature despite the title. They act as a symbol of the wild, but as we are repeatedly told, they seldom attack humans.
Stef Penney grew up in Edinburgh and studied at Bristol University (my old alma mater) before studying film and TV at the excellent College of Art here in Bournemouth. She was picked up by Carlton Television's New Writers scheme and has written and directed two films. She has never been to Canada and, like Karl Marx before her, did all her research in the British Library. (Why should that surprise us? Had Isaac Asimov ever been to outer space?) She has at least one anachronism: the town of Kitchener was named after the General; in 1867 it was called Berlin.
Mostly things resolve themselves, but with so many plot lines and over 50 characters there are some loose ends. What did happen to Amy Seton? Why was Jammet killed? What was Mrs Ross's first name? (Look away now if you don't want to see the spoilers) The answer to the last is Lucy as can be worked out from pages 165 and 170 and indeed from the final page. Jammet was killed because to prevent him taking what others covered and Amy Seton is surely the subject of another book, just as Mrs Ross's prequel is already the subject of a screenplay.
Thursday, September 06, 2007
Playing Solitaire and learning from games
I have several games of patience on my computer. They are addictive and when I have a spare minute I often play a game. I limit myself. It teaches me discipline. One game only, then I leave it.
One of them, 'Spider Solitaire', is very difficult at the highest level and I win only once in a hundred times. You are called upon to make decisions. Shall I put that '6' or the other '6' on the '7'? When you see the result of your decision, you often wish you had made a different choice. But there is no going back. There is no point in worrying about the 'what ifs?' and the 'might have beens'. That's like life. We can be disappointed in the decisions we have made but the decisions can't be undone. We have to learn to live with them. Sometimes there is no choice; there is only one '6' to put on one '7'. If life turns out badly as a consequence we have nothing to reproach ourselves with, and even if there were a choice and there were no indicators to guide a choice, then it wasn't our fault if we made the wrong one.
'Free Cell' is a different type of solitaire. Supposedly it will always come out if we make the right choices. Of course, we often make wrong ones, but the game has the facility to be replayed. Sometimes I have nine or ten attempts before I make the right choices. Life isn't like that. It's not like 'Groundhog Day' where we replay the same day thousands of times before we finally get the girl. We only have one try and have to live with the consequences. 'Free Cell' is a more interesting puzzle, but 'Spider' is truer to life.
Winning isn't everything. Cricket teaches that. At least it used to. When I played I remember being told off by the captain for kicking the ball away in frustration when I had made a silly mistake. "That's not how we play the game."
Perhaps golf is a better model or snooker; game where you call your own fouls. Too much today sport is too much about winning. Athletes who build up their bodies with drugs, cyclists who increase their hemoglobin with EPO, footballers who foul behind the referee's back, cricketers who 'sledge' their opponents; what is the point of cheating to win? Recently Diego Maradona, the extremely gifted Argentinian footballer, appeared on a chat show run by Hugo Chavez. Together they celebrated the famous 'hand-of-God' goal that enabled the Argentinians to defeat England in the World Cup. Cheating may have gained Maradona a World Cup winner's medal, but today he is a fat, cocaine addicted failure. A price not worth paying?
What is fame? An empty bubble;
Gold? A transient, shining trouble
Fame is a food that dead men eat,-
I have no stomach for such meat.
Call me old-fashioned, but I prefer:
There’s a breathless hush in the close tonight
Ten to make and the match to win
A bumping pitch and a blinding light
An hour to play and the last man in
And it’s not for the sake of a ribboned coat
Or the selfish hope of a season’s fame
But his Captain’s hand on his shoulder smote –
‘Play up! Play up! And play the game!’
One of them, 'Spider Solitaire', is very difficult at the highest level and I win only once in a hundred times. You are called upon to make decisions. Shall I put that '6' or the other '6' on the '7'? When you see the result of your decision, you often wish you had made a different choice. But there is no going back. There is no point in worrying about the 'what ifs?' and the 'might have beens'. That's like life. We can be disappointed in the decisions we have made but the decisions can't be undone. We have to learn to live with them. Sometimes there is no choice; there is only one '6' to put on one '7'. If life turns out badly as a consequence we have nothing to reproach ourselves with, and even if there were a choice and there were no indicators to guide a choice, then it wasn't our fault if we made the wrong one.
'Free Cell' is a different type of solitaire. Supposedly it will always come out if we make the right choices. Of course, we often make wrong ones, but the game has the facility to be replayed. Sometimes I have nine or ten attempts before I make the right choices. Life isn't like that. It's not like 'Groundhog Day' where we replay the same day thousands of times before we finally get the girl. We only have one try and have to live with the consequences. 'Free Cell' is a more interesting puzzle, but 'Spider' is truer to life.
Winning isn't everything. Cricket teaches that. At least it used to. When I played I remember being told off by the captain for kicking the ball away in frustration when I had made a silly mistake. "That's not how we play the game."
Perhaps golf is a better model or snooker; game where you call your own fouls. Too much today sport is too much about winning. Athletes who build up their bodies with drugs, cyclists who increase their hemoglobin with EPO, footballers who foul behind the referee's back, cricketers who 'sledge' their opponents; what is the point of cheating to win? Recently Diego Maradona, the extremely gifted Argentinian footballer, appeared on a chat show run by Hugo Chavez. Together they celebrated the famous 'hand-of-God' goal that enabled the Argentinians to defeat England in the World Cup. Cheating may have gained Maradona a World Cup winner's medal, but today he is a fat, cocaine addicted failure. A price not worth paying?
What is fame? An empty bubble;
Gold? A transient, shining trouble
Fame is a food that dead men eat,-
I have no stomach for such meat.
Call me old-fashioned, but I prefer:
There’s a breathless hush in the close tonight
Ten to make and the match to win
A bumping pitch and a blinding light
An hour to play and the last man in
And it’s not for the sake of a ribboned coat
Or the selfish hope of a season’s fame
But his Captain’s hand on his shoulder smote –
‘Play up! Play up! And play the game!’
Wednesday, September 05, 2007
Boys' Toys
Apparently, Top Gear, the Jeremy Clarkson program about fast cars and boys' toys, is sold to 200 different countries and is even more popular in America than it is here. I write about it because my son, the engineer, is taking part in the program they are currently making. They are entering a car that they have built for a 24-hour race at Silverstone and my son has done the brakes. He was there today at the track, but the car was in limp-home mode and wouldn't go above 3000 revs.
Jeremy Clarkson is very tall (6ft 4) and comes across as a chain-smoking, coca-cola swilling curmudgeon who is waited on hand and foot by young girl PAs. It is probably an act; I am sure in the privacy of his home he is meekness personified and kind to pigeons. Richard Hammond is only 5ft 4 and so when they change drivers the seat has to be mightily adjusted and a new seat-belt fitted. James May is reputedly a terrible driver who has to be coached by Jackie Stewart when they drive fact cars. The Stig is no longer Perry ****** (I dare not reveal his new identity for fear of assassination). the first Stig was sacked when he revealed his name to a Sunday paper. He now runs a racing driver school in America. The new Stig is awesomely fast.
Jeremy Clarkson is very tall (6ft 4) and comes across as a chain-smoking, coca-cola swilling curmudgeon who is waited on hand and foot by young girl PAs. It is probably an act; I am sure in the privacy of his home he is meekness personified and kind to pigeons. Richard Hammond is only 5ft 4 and so when they change drivers the seat has to be mightily adjusted and a new seat-belt fitted. James May is reputedly a terrible driver who has to be coached by Jackie Stewart when they drive fact cars. The Stig is no longer Perry ****** (I dare not reveal his new identity for fear of assassination). the first Stig was sacked when he revealed his name to a Sunday paper. He now runs a racing driver school in America. The new Stig is awesomely fast.
Monday, September 03, 2007
Charlotte Gray
I have been reading 'Charlotte Gray' over the past week. Sebastian Faulkes is sometimes regarded as the greatest living English novelist, but that is over-egging the pudding. I had previously read 'Birdsong' which was a flawed masterpiece, but in this one he has worked hard on making the flaws more apparent. For a start the plot is preposterous. He concentrates so much on the countryside that you don't notice how silly the plot is at first, but on reflection the story was so full of unlikely co-incidences as to detract from giving it serious consideration.
His style is to report scenes in great detail, but this detracts from pace, and if a book about the French resistance needs anything it needs pace. about half way through I doubted whether I could find the energy to finish it. Several characters form his earlier books make cameo appearances in this one, but whether this adds to the book, I doubt. Perhaps I am so accustomed to the Holocaust that the details no longer shock, so that the sections that dealt with the arrest of Levade and the deportation of the two little boys never really held my attention. Wost of all was the character of Charlotte Gray. Perhaps Kate Blanchett could make something of her in the film, but I just though she was a silly and headstrong child who needed her bottom smacked. The Spitfire pilot was thinly drawn and the most interesting character, Charlotte's father made only a brief appearance. I am afraid that the real problem is that the characters don't emerge from the page.
His style is to report scenes in great detail, but this detracts from pace, and if a book about the French resistance needs anything it needs pace. about half way through I doubted whether I could find the energy to finish it. Several characters form his earlier books make cameo appearances in this one, but whether this adds to the book, I doubt. Perhaps I am so accustomed to the Holocaust that the details no longer shock, so that the sections that dealt with the arrest of Levade and the deportation of the two little boys never really held my attention. Wost of all was the character of Charlotte Gray. Perhaps Kate Blanchett could make something of her in the film, but I just though she was a silly and headstrong child who needed her bottom smacked. The Spitfire pilot was thinly drawn and the most interesting character, Charlotte's father made only a brief appearance. I am afraid that the real problem is that the characters don't emerge from the page.
Sunday, September 02, 2007
Prayer
In the Garden of Gethsemane the closest disciples of Jesus fell asleep when they were supposed to be praying. "Watch and pray," commanded Jesus, but three times he came back and found them slumbering.
If Peter, James and John couldn't hack it, what hope is there for you and me?
Why don't we pray? I have to admit that my prayer life is perfunctory; that I frequently get distracted and often fall asleep. Why is that?
First, it is because we are not really convinced that it is necessary. We take the view that God will run His universe without my help; that any advice I could give Him would be bound to be flawed; that we are beyond the shopping-list type of prayer of our childhood. In what sort of way could we change God's mind? Is God likely to re-order the world at our insistence? Is He not sovereign?
In this we are profoundly mistaken. Remember Abraham above Sodom. In a comical story reminiscent of Del Boy and Rodney (Google Only Fools and Horses if you don't get the reference) he beats God down to only 10 righteous men necessary to spare the city. Of course, God still destroys Sodom, but it demonstrates that He doesn't have a closed mind. Remember also James, "The prayer of a righteous man is powerful and effective."
The fact is that we cannot use our small minds to second guess God's will. The apparent conflict between God's sovereignty and human responsibility cannot be sorted out by us; the fact is that both are taught in the Bible and both are true. God's will will be done, but we are also commanded to pray. It seems that in some way God's will will only be done in the context of prayer.
Second, we are in a spiritual battle. "The devil trembles when he sees the weakest saint upon his knees". Consequently, he puts every obstruction possible in our way.
It is our responsibility to play our part in this battle and not to be distracted. We are only strong in that we pray. We are puny foes for the devil when we stand unaided, but when we stand with God we are invincible. Remember the story of Elisha surrounded by the army of Aram and how he said to his servant, "Don't be afraid, those that are with us are more than those who are with them." And he asked the Lord to open his servant's eyes so that he could see the hills full of horses and chariots of fire.
Third, we make excuses. It is not my gift. I cannot pray in public. I am shy. I am afraid of making a fool of myself. I am sure to come out with some terrible heresy. Prayer is not a gift, it is a responsibility. Everyone can pray and it is not a competition.
Fourth, we are tired. Just as the disciples at Gethsemane were tired we often choose the most inopportune moments to pray. If I get into bed late at night and expect to be able to pray I am doomed to failure.
We miss out on so much when we do not pray, and we deny our friends and family God's blessing. If we do not pray for our family, who will? If we do not pray for our friends will anyone else? If we do not pray for our city, will it stand? If we do not pray for our country, no wonder our politicians get caught in sex scandals and financial scams; no wonder our television is so revolting; no wonder our kids go astray; no wonder our influence in the world is declining; no wonder abortions are burgeoning; no wonder so many families are falling apart; no wonder young men are killing each other on street corners; no wonder babies are born addicted to crack cocaine; no wonder our prisons are full.
Prayer is the lifeblood of the church. What is the church for? The church is there to pray. CH Spurgeon, the greatest preacher of the Nineteenth Century was asked the secret of his success. "My people pray for me," was his reply.
Pray for your leaders, pray for your church, pray for the sick, pray for those with responsibility for traffic, air traffic controllers, sewerage workers and garbage men, prison officers and policemen, those in the armed services, firemen, nurses, doctors, teachers, even lawyers. Pray for those in government, those in the House and Senate, those facing testing, those who are sinning; pray for thieves and murderers, adulterers and homosexuals; pray for the angry, the hurting, the betrayed and those who betray; pray for widows and orphans, pray for refugees, pray for the homeless; pray for those without work, those without funds, pray for the sick.
This is such important work, make it a priority. Make lists. And give thanks. Today I examined a flower in my garden. In several shades of pink my gladioli attract the bees, but there was no need for them to be beautiful too. God did it to please me. God made a wonderful world for me. He gave me all the food I need. He gave me an interesting life with much to fire my imagination. He gave me beauty to appreciate and wonderful music. But this was not enough. Knowing that I would rebel; knowing that I would disobey Him, He sent His son to die for me, to pay the price of my felonies so that I should not perish but have everlasting life. He sent His Spirit to awaken this dead soul and make me aware of Jesus and gave me all I need for salvation. Before you start praying, praise Him for His glorious majesty and thank Him for his magnificent grace.
If Peter, James and John couldn't hack it, what hope is there for you and me?
Why don't we pray? I have to admit that my prayer life is perfunctory; that I frequently get distracted and often fall asleep. Why is that?
First, it is because we are not really convinced that it is necessary. We take the view that God will run His universe without my help; that any advice I could give Him would be bound to be flawed; that we are beyond the shopping-list type of prayer of our childhood. In what sort of way could we change God's mind? Is God likely to re-order the world at our insistence? Is He not sovereign?
In this we are profoundly mistaken. Remember Abraham above Sodom. In a comical story reminiscent of Del Boy and Rodney (Google Only Fools and Horses if you don't get the reference) he beats God down to only 10 righteous men necessary to spare the city. Of course, God still destroys Sodom, but it demonstrates that He doesn't have a closed mind. Remember also James, "The prayer of a righteous man is powerful and effective."
The fact is that we cannot use our small minds to second guess God's will. The apparent conflict between God's sovereignty and human responsibility cannot be sorted out by us; the fact is that both are taught in the Bible and both are true. God's will will be done, but we are also commanded to pray. It seems that in some way God's will will only be done in the context of prayer.
Second, we are in a spiritual battle. "The devil trembles when he sees the weakest saint upon his knees". Consequently, he puts every obstruction possible in our way.
It is our responsibility to play our part in this battle and not to be distracted. We are only strong in that we pray. We are puny foes for the devil when we stand unaided, but when we stand with God we are invincible. Remember the story of Elisha surrounded by the army of Aram and how he said to his servant, "Don't be afraid, those that are with us are more than those who are with them." And he asked the Lord to open his servant's eyes so that he could see the hills full of horses and chariots of fire.
Third, we make excuses. It is not my gift. I cannot pray in public. I am shy. I am afraid of making a fool of myself. I am sure to come out with some terrible heresy. Prayer is not a gift, it is a responsibility. Everyone can pray and it is not a competition.
Fourth, we are tired. Just as the disciples at Gethsemane were tired we often choose the most inopportune moments to pray. If I get into bed late at night and expect to be able to pray I am doomed to failure.
We miss out on so much when we do not pray, and we deny our friends and family God's blessing. If we do not pray for our family, who will? If we do not pray for our friends will anyone else? If we do not pray for our city, will it stand? If we do not pray for our country, no wonder our politicians get caught in sex scandals and financial scams; no wonder our television is so revolting; no wonder our kids go astray; no wonder our influence in the world is declining; no wonder abortions are burgeoning; no wonder so many families are falling apart; no wonder young men are killing each other on street corners; no wonder babies are born addicted to crack cocaine; no wonder our prisons are full.
Prayer is the lifeblood of the church. What is the church for? The church is there to pray. CH Spurgeon, the greatest preacher of the Nineteenth Century was asked the secret of his success. "My people pray for me," was his reply.
Pray for your leaders, pray for your church, pray for the sick, pray for those with responsibility for traffic, air traffic controllers, sewerage workers and garbage men, prison officers and policemen, those in the armed services, firemen, nurses, doctors, teachers, even lawyers. Pray for those in government, those in the House and Senate, those facing testing, those who are sinning; pray for thieves and murderers, adulterers and homosexuals; pray for the angry, the hurting, the betrayed and those who betray; pray for widows and orphans, pray for refugees, pray for the homeless; pray for those without work, those without funds, pray for the sick.
This is such important work, make it a priority. Make lists. And give thanks. Today I examined a flower in my garden. In several shades of pink my gladioli attract the bees, but there was no need for them to be beautiful too. God did it to please me. God made a wonderful world for me. He gave me all the food I need. He gave me an interesting life with much to fire my imagination. He gave me beauty to appreciate and wonderful music. But this was not enough. Knowing that I would rebel; knowing that I would disobey Him, He sent His son to die for me, to pay the price of my felonies so that I should not perish but have everlasting life. He sent His Spirit to awaken this dead soul and make me aware of Jesus and gave me all I need for salvation. Before you start praying, praise Him for His glorious majesty and thank Him for his magnificent grace.
Saturday, September 01, 2007
In England Now
Little blogging this week, mainly because I have been doing my accounts for the tax man. This is the task that I hate the most. I suppose I should do them as I go, then I wouldn't have to try and remember what exactly that item 'Staples £3-98' actually was.
I won't comment more about the task except to say it might have been worse; I could be an accountant.
This has been the worst summer in England since 1956, though that did have some redeeming features. We retained the Ashes against Australia and Jim Laker took 19-90 at Old Trafford. No sporting redemption this year; the cricketers have lost to India, the rugby players have lost to France, the footballers have been struggling, the tennis players are out of form, and the only athlete to win a gold medal at the IAAF World Championships is someone who missed three off-season drug-testing appointments.
Blair has gone and we gave had a summer of Brown. What is it like in England now?
We have had a lot of floods. Brown has handled the press well; he hasn't fallen into the traps set for Bush over Katrina. He was helped by David Cameron fulfilling a long planned foreign trip while his own constituency was under water. The reasons for the floods - too much house building without the necessary infrastructure - can hardly be laid at the feet of an incoming prime minister.
The economy remains strong; although the 'footsie' fell with the American sub-prime crisis, it seems to have recovered and stabilized. The cash-for-honors crisis seems to have gone quiet - I suppose it is regarded as Tony Blair's dirty washing. John Prescott, the boorish Deputy Prime Minister and constant source of embarrassment has gone too. There have been no financial or sexual scandals surrounding Brown.
The big test, of course, remains Iraq. He packed his cabinet with Bush-haters, yet seemed amiable enough when he visited Camp David, pledging friendship and support. While the surge seems to be showing some benefit in the north, the carnage has got worse in Basra. There has been criticism of the British forces in the south from some of the American armchair generals (I suppose in Patrick O'Brien's world they would be Admirals of the Yellow). In the press today are rejoinders by retired British Generals blaming Rumsfeld for the whole sorry mess.
Of course, the situation in Iraq is more complex than we are told. The success of the surge is related to the war against Al-Qaeda. The Americans have successfully separated Sunni leaders from the Sunni Al-Qaeda and have begun to undo the mistake of assuming that all Saddam supporters were fervent Baathists. They were careerists backing the winning horse. In the south Al-Qaeda is not a factor; they are all Shi'ites. The question there is how much influence Iran will have over their fellow Shi'ites. The anti-Iran conflict is a particularly American one that the British have never fully bought in to. I can understand that Americans still want pay-back for the hostage crisis of the 1970s and don't trust the Ayatollahs but in the real world you have to deal with things as they are, not how you would like them to be.
The truth is that politics in Basra is unlike anything in the West since Al Capone was defeated in Chicago. Unless there is a serious intention of recreating the Untouchables, and there is no political mandate or will to do that, we are better off out of there.
We hear of a six-month truce from the Mahdi army. Presumably some sort of deal has been done between Muqtada al Sadr and the British Foreign Office. You want us to leave and we want to leave. We can't go if there are IEDs going off every day. Give us some peace and quiet and we will declare that we have successfully handed over to Iraqi forces, which, as you know, are largely manned by your militia. Why would he demur?
Afghanistan is also a problem. There are criticisms that the government has sent men out to fight with inadequate equipment - a charge that can be laid at Brown's door since the ex-chancellor may well have penny-pinched on the Army budget. The poppy harvest has not been reduced. Again, I see the hand of the Foreign Office here. There is a worldwide shortage of morphine, so it makes no sense to reduce the source of the raw material. Winning the battle against the Taliban means winning hearts and minds. You hardly deny the Taliban a sanctuary by making the farmers who could hide them penniless.
At home there is a crisis in the prisons. Because they are overflowing they are letting prisoners out two weeks earlier than they should. One newspaper is keeping a record of new crimes committed by prisoners so-released. 59 so far. Crime statistics are so easily manipulated as to be meaningless. The government spins them to put themselves in the best light. Concealed in the current figures is a fourfold increase in the numbers of killings and injury from guns. One Chief Constable defends the figures because they are nothing like as bad as in American cities. But owning guns is illegal in the UK and legal in America. Of course, it is not as bad, but it's not comparing like with like. With the police so defeatist what can you expect?
Brown has a 10 point lead in the polls and might call an early election apart from one thing - Europe. The European Constitution was defeated by referenda in France and Holland. Tony Blair had promised a referendum, but didn't have to deliver because the whole thing was hit into the long grass by the French and Dutch defeats. The European leaders had a second go and produced a 'Treaty' that is 95% the same as the Constitution. This does not require a referendum they said it can be agreed by local parliaments. Brown has told us we won't have a referendum, but a large majority of the public want one and a large majority would vote against. If he were to call an election now, it would become in effect a referendum on Europe, which he would certainly lose despite his lead in the Opinion Polls. So no election yet, I think.
Oh, and Barclays are in trouble since I took my money out and transferred it to teh Halifax.
I won't comment more about the task except to say it might have been worse; I could be an accountant.
This has been the worst summer in England since 1956, though that did have some redeeming features. We retained the Ashes against Australia and Jim Laker took 19-90 at Old Trafford. No sporting redemption this year; the cricketers have lost to India, the rugby players have lost to France, the footballers have been struggling, the tennis players are out of form, and the only athlete to win a gold medal at the IAAF World Championships is someone who missed three off-season drug-testing appointments.
Blair has gone and we gave had a summer of Brown. What is it like in England now?
We have had a lot of floods. Brown has handled the press well; he hasn't fallen into the traps set for Bush over Katrina. He was helped by David Cameron fulfilling a long planned foreign trip while his own constituency was under water. The reasons for the floods - too much house building without the necessary infrastructure - can hardly be laid at the feet of an incoming prime minister.
The economy remains strong; although the 'footsie' fell with the American sub-prime crisis, it seems to have recovered and stabilized. The cash-for-honors crisis seems to have gone quiet - I suppose it is regarded as Tony Blair's dirty washing. John Prescott, the boorish Deputy Prime Minister and constant source of embarrassment has gone too. There have been no financial or sexual scandals surrounding Brown.
The big test, of course, remains Iraq. He packed his cabinet with Bush-haters, yet seemed amiable enough when he visited Camp David, pledging friendship and support. While the surge seems to be showing some benefit in the north, the carnage has got worse in Basra. There has been criticism of the British forces in the south from some of the American armchair generals (I suppose in Patrick O'Brien's world they would be Admirals of the Yellow). In the press today are rejoinders by retired British Generals blaming Rumsfeld for the whole sorry mess.
Of course, the situation in Iraq is more complex than we are told. The success of the surge is related to the war against Al-Qaeda. The Americans have successfully separated Sunni leaders from the Sunni Al-Qaeda and have begun to undo the mistake of assuming that all Saddam supporters were fervent Baathists. They were careerists backing the winning horse. In the south Al-Qaeda is not a factor; they are all Shi'ites. The question there is how much influence Iran will have over their fellow Shi'ites. The anti-Iran conflict is a particularly American one that the British have never fully bought in to. I can understand that Americans still want pay-back for the hostage crisis of the 1970s and don't trust the Ayatollahs but in the real world you have to deal with things as they are, not how you would like them to be.
The truth is that politics in Basra is unlike anything in the West since Al Capone was defeated in Chicago. Unless there is a serious intention of recreating the Untouchables, and there is no political mandate or will to do that, we are better off out of there.
We hear of a six-month truce from the Mahdi army. Presumably some sort of deal has been done between Muqtada al Sadr and the British Foreign Office. You want us to leave and we want to leave. We can't go if there are IEDs going off every day. Give us some peace and quiet and we will declare that we have successfully handed over to Iraqi forces, which, as you know, are largely manned by your militia. Why would he demur?
Afghanistan is also a problem. There are criticisms that the government has sent men out to fight with inadequate equipment - a charge that can be laid at Brown's door since the ex-chancellor may well have penny-pinched on the Army budget. The poppy harvest has not been reduced. Again, I see the hand of the Foreign Office here. There is a worldwide shortage of morphine, so it makes no sense to reduce the source of the raw material. Winning the battle against the Taliban means winning hearts and minds. You hardly deny the Taliban a sanctuary by making the farmers who could hide them penniless.
At home there is a crisis in the prisons. Because they are overflowing they are letting prisoners out two weeks earlier than they should. One newspaper is keeping a record of new crimes committed by prisoners so-released. 59 so far. Crime statistics are so easily manipulated as to be meaningless. The government spins them to put themselves in the best light. Concealed in the current figures is a fourfold increase in the numbers of killings and injury from guns. One Chief Constable defends the figures because they are nothing like as bad as in American cities. But owning guns is illegal in the UK and legal in America. Of course, it is not as bad, but it's not comparing like with like. With the police so defeatist what can you expect?
Brown has a 10 point lead in the polls and might call an early election apart from one thing - Europe. The European Constitution was defeated by referenda in France and Holland. Tony Blair had promised a referendum, but didn't have to deliver because the whole thing was hit into the long grass by the French and Dutch defeats. The European leaders had a second go and produced a 'Treaty' that is 95% the same as the Constitution. This does not require a referendum they said it can be agreed by local parliaments. Brown has told us we won't have a referendum, but a large majority of the public want one and a large majority would vote against. If he were to call an election now, it would become in effect a referendum on Europe, which he would certainly lose despite his lead in the Opinion Polls. So no election yet, I think.
Oh, and Barclays are in trouble since I took my money out and transferred it to teh Halifax.
Tuesday, August 28, 2007
Why doesn't God stop it?
Anthony Walker, an 18-year old college student, promising athlete, and devout Christian, was hacked down and killed by racist, Michael Barton. Where was God?
Dr Victoria Anyetei was stabbed in a frenzied attack in her own car before she left for work. She was a devout Christian. Where was God?
Gerry Tobin, 35, was killed with a shot to the back of the head as he drove his Harley-Davidson in Warwickshire. He was a member of Hell’s Angels but surprisingly according to the Times he was a Christian who used to hold Bible classes and prayer meetings and dreamt of being a missionary. Where was God?
A post mortem at Kingston Mortuary on Friday showed that 51-year old Egyptian born Christian Mrs Leila Rezk died from severe head injuries, and police say the killer may have murdered her with his bare hands. Where was God?
Failed asylum seeker Kamel Bourgass was jailed for 22 years for stabbing to death Detective Constable Stephen Oake. Constable Oake was a keen evangelical Christian. Where was God?
All these took place in peaceful England in recent months; in a supposedly Christian country where persecution is said to be a thing of the past.
It is worse elsewhere: Twenty-three South Korean Christians have been captured by the Taliban; two of them murdered; the rest held hostage.
Where is God in Afghanistan?
In Iraq it is horrible for everyone, but especially so for Christians. Assyrian Christians, who belong to the Syrian Orthodox Church and a number of other small, ancient Churches, worship in (and sometimes speak) the mother tongue of Jesus, Aramaic. The Allied intervention in Iraq has made the plight of the Assyrians infinitely worse but it was under the vile dictatorship of Saddam Husain that the ethnic cleansing of Assyrians began. "Saddam destroyed over 200 of our towns and villages, but with our very limited resources, we have rebuilt hundreds of homes," says a spokesman for the Assyrian Aid Society.
"When they cook a dish in the Middle East, it is traditional to put the meat on top of the rice when they serve it. They kidnapped a woman’s baby in Baghdad, a toddler, and because the mother was unable to pay the ransom, they returned her child – beheaded, roasted and served on a mound of rice. The infant’s crime was to be an Assyrian.
Since the invasion of Iraq, Muslim militants have bombed 28 churches and murdered hundreds of Christians. Last October, Islamists beheaded a priest in Mosul.
Where is God in Iraq?
It is not only Muslims who are terrorizing Christians: On June 2, police found the body of Isaac Raju just outside the state capital of Hyderabad in southern India. The independent church pastor had been missing since May 24. On May 21, the body of K. Daniel, a preacher from Kummarvadi, also was found on the outskirts of Hyderabad. Miliant Hindus are active in several parts of India.
Where is God in India?
Where is the God who could feed five thousand with a few loaves and fishes? Where is the God who walked on water, made the blind man see, turned water into wine, and raised the dead? We know and are convinced that the God of Abraham, Isaac and Jacob; the God who brought the Children of Israel out of Egypt; the God who defeated the prophets of Baal on Carmel; the God who saved the three lads from the burning fiery furnace in Babylon and stopped the mouths of the lions; the God who raised the Lord Jesus Christ from the dead, can work miracles. When He sees His church suffering in this way, why doesn’t He intervene?
In Mark chapter 13 we begin to see an answer. Jesus warned his disciples that something was coming to Jerusalem that would mean ‘days of distress unequaled from the beginning…until now, and never to be equaled again.’
Auschwitz was terrible; the Bible says this was worse. Hiroshima was awful; the Bible says this was worse. The trenches at the Somme and Ypres were horrible; the Bible says this was worse.
In April 66AD the Romans surrounded Jerusalem. The city was full; it was Passover time. Soon food grew short. People were eating dung. If they tried to escape the Romans crucified them. If they surrendered, they were cut open with knives as the Romans searched for hidden jewels and coins. If they stayed put they starved. Women began to kill and cook their children. Over one million one hundred thousand people died. A mere 92,000 survived to be sold into slavery. The city was razed to the ground. Why did God not intervene? But He did. He told them to pray that it would not happen in winter. The Christians prayed and their prayer was answered; it happened in summer. He warned them to flee. The Christians remembered and they fled. There were few if any Christians left in Jerusalem when the Romans arrived. And He shortened the days. There is no objective proof of that. But often when we complain that God has not intervened we may be unaware that He has shortened the days.
God has made an ordered Universe. The Law of Gravity is the Law of God. Boyle’s Law was God’s law first. God is not the Lord of chaos and disorder. The scientist of old used to say that they were ‘thing God’s thoughts after Him’. They would not have got far had He kept changing His mind as the measured.
Miracles are rare – even in Biblical times; just Joseph, Moses, Joshua, Elijah, Elisha, Jonah, Daniel, Jesus and the Apostles. He doesn’t feed our greed; He doesn’t pander to our pride; miracles display the Glory of God.
Despite what the tele-evangelists tell you, things will not be hunky-dory when you come to Christ. You won’t have an easy life if you slip $10 in an envelope and send it to Elmer Gantry Inc. No tented mission will make the blind see, the lame walk or the dead rise. False Christs and false prophets will appear and perform signs and miracles to deceive the elect – if that were possible. No, we are told that in this world we will have tribulation. This wasn’t a lame threat; it was a promise.
We must be prepared for trouble.
First we must understand the Bible. Verse 14: ‘Let the reader understand’ not an aside from Mark, but an instruction from Jesus. God has revealed Himself in scripture. We must read and understand if we want to know His mind.
Then we must do what we can. Don’t go on your roof when a storm is coming. If you were fleeing a burning building you would be mad to go back for your computer or a painting you liked. We might be persecuted but there is no need to invite trouble. Don’t go into a Mosque and condemn Muhammad.
Then we must pray. Don’t be a fatalist. God is moved by prayer; moved but not manipulated. Sometimes His ends will be achieved in a different way because we pray. He is a good God. We are sometimes blind to the hand of God in the affairs of Man. Who knows how many times he has ‘shortened the days’.
In the Second World War who stayed Hitler’s hand while 300,000 British and French soldiers escaped from the beaches of Dunkirk? Who provided the cloud cover that kept the attacking Stukas from bombing vulnerable men on the beaches? And how often has disaster ensued because no-one prayed?
How could ten Godly men have saved Sodom? They would have prayed. Why did Jonah take ship for Tarshish? Because he knew that if he preached to the men of Nineveh they might repent and God forgive them. God is like that. He is not willing that any should perish but that all should turn from their wicked ways and live.
In Nineveh there were one hundred and twenty thousand people who did not know their left hand from their right. Should our God not have compassion on them? How about the people of Kandarha or Khartoum or Basra or Baghdad or Hyderabad or Harare?
Dr Victoria Anyetei was stabbed in a frenzied attack in her own car before she left for work. She was a devout Christian. Where was God?
Gerry Tobin, 35, was killed with a shot to the back of the head as he drove his Harley-Davidson in Warwickshire. He was a member of Hell’s Angels but surprisingly according to the Times he was a Christian who used to hold Bible classes and prayer meetings and dreamt of being a missionary. Where was God?
A post mortem at Kingston Mortuary on Friday showed that 51-year old Egyptian born Christian Mrs Leila Rezk died from severe head injuries, and police say the killer may have murdered her with his bare hands. Where was God?
Failed asylum seeker Kamel Bourgass was jailed for 22 years for stabbing to death Detective Constable Stephen Oake. Constable Oake was a keen evangelical Christian. Where was God?
All these took place in peaceful England in recent months; in a supposedly Christian country where persecution is said to be a thing of the past.
It is worse elsewhere: Twenty-three South Korean Christians have been captured by the Taliban; two of them murdered; the rest held hostage.
Where is God in Afghanistan?
In Iraq it is horrible for everyone, but especially so for Christians. Assyrian Christians, who belong to the Syrian Orthodox Church and a number of other small, ancient Churches, worship in (and sometimes speak) the mother tongue of Jesus, Aramaic. The Allied intervention in Iraq has made the plight of the Assyrians infinitely worse but it was under the vile dictatorship of Saddam Husain that the ethnic cleansing of Assyrians began. "Saddam destroyed over 200 of our towns and villages, but with our very limited resources, we have rebuilt hundreds of homes," says a spokesman for the Assyrian Aid Society.
"When they cook a dish in the Middle East, it is traditional to put the meat on top of the rice when they serve it. They kidnapped a woman’s baby in Baghdad, a toddler, and because the mother was unable to pay the ransom, they returned her child – beheaded, roasted and served on a mound of rice. The infant’s crime was to be an Assyrian.
Since the invasion of Iraq, Muslim militants have bombed 28 churches and murdered hundreds of Christians. Last October, Islamists beheaded a priest in Mosul.
Where is God in Iraq?
It is not only Muslims who are terrorizing Christians: On June 2, police found the body of Isaac Raju just outside the state capital of Hyderabad in southern India. The independent church pastor had been missing since May 24. On May 21, the body of K. Daniel, a preacher from Kummarvadi, also was found on the outskirts of Hyderabad. Miliant Hindus are active in several parts of India.
Where is God in India?
Where is the God who could feed five thousand with a few loaves and fishes? Where is the God who walked on water, made the blind man see, turned water into wine, and raised the dead? We know and are convinced that the God of Abraham, Isaac and Jacob; the God who brought the Children of Israel out of Egypt; the God who defeated the prophets of Baal on Carmel; the God who saved the three lads from the burning fiery furnace in Babylon and stopped the mouths of the lions; the God who raised the Lord Jesus Christ from the dead, can work miracles. When He sees His church suffering in this way, why doesn’t He intervene?
In Mark chapter 13 we begin to see an answer. Jesus warned his disciples that something was coming to Jerusalem that would mean ‘days of distress unequaled from the beginning…until now, and never to be equaled again.’
Auschwitz was terrible; the Bible says this was worse. Hiroshima was awful; the Bible says this was worse. The trenches at the Somme and Ypres were horrible; the Bible says this was worse.
In April 66AD the Romans surrounded Jerusalem. The city was full; it was Passover time. Soon food grew short. People were eating dung. If they tried to escape the Romans crucified them. If they surrendered, they were cut open with knives as the Romans searched for hidden jewels and coins. If they stayed put they starved. Women began to kill and cook their children. Over one million one hundred thousand people died. A mere 92,000 survived to be sold into slavery. The city was razed to the ground. Why did God not intervene? But He did. He told them to pray that it would not happen in winter. The Christians prayed and their prayer was answered; it happened in summer. He warned them to flee. The Christians remembered and they fled. There were few if any Christians left in Jerusalem when the Romans arrived. And He shortened the days. There is no objective proof of that. But often when we complain that God has not intervened we may be unaware that He has shortened the days.
God has made an ordered Universe. The Law of Gravity is the Law of God. Boyle’s Law was God’s law first. God is not the Lord of chaos and disorder. The scientist of old used to say that they were ‘thing God’s thoughts after Him’. They would not have got far had He kept changing His mind as the measured.
Miracles are rare – even in Biblical times; just Joseph, Moses, Joshua, Elijah, Elisha, Jonah, Daniel, Jesus and the Apostles. He doesn’t feed our greed; He doesn’t pander to our pride; miracles display the Glory of God.
Despite what the tele-evangelists tell you, things will not be hunky-dory when you come to Christ. You won’t have an easy life if you slip $10 in an envelope and send it to Elmer Gantry Inc. No tented mission will make the blind see, the lame walk or the dead rise. False Christs and false prophets will appear and perform signs and miracles to deceive the elect – if that were possible. No, we are told that in this world we will have tribulation. This wasn’t a lame threat; it was a promise.
We must be prepared for trouble.
First we must understand the Bible. Verse 14: ‘Let the reader understand’ not an aside from Mark, but an instruction from Jesus. God has revealed Himself in scripture. We must read and understand if we want to know His mind.
Then we must do what we can. Don’t go on your roof when a storm is coming. If you were fleeing a burning building you would be mad to go back for your computer or a painting you liked. We might be persecuted but there is no need to invite trouble. Don’t go into a Mosque and condemn Muhammad.
Then we must pray. Don’t be a fatalist. God is moved by prayer; moved but not manipulated. Sometimes His ends will be achieved in a different way because we pray. He is a good God. We are sometimes blind to the hand of God in the affairs of Man. Who knows how many times he has ‘shortened the days’.
In the Second World War who stayed Hitler’s hand while 300,000 British and French soldiers escaped from the beaches of Dunkirk? Who provided the cloud cover that kept the attacking Stukas from bombing vulnerable men on the beaches? And how often has disaster ensued because no-one prayed?
How could ten Godly men have saved Sodom? They would have prayed. Why did Jonah take ship for Tarshish? Because he knew that if he preached to the men of Nineveh they might repent and God forgive them. God is like that. He is not willing that any should perish but that all should turn from their wicked ways and live.
In Nineveh there were one hundred and twenty thousand people who did not know their left hand from their right. Should our God not have compassion on them? How about the people of Kandarha or Khartoum or Basra or Baghdad or Hyderabad or Harare?
Friday, August 24, 2007
News from the Barnabus Trust
In the Dora region of Baghdad Iraqi Christians are being forced to pay jizya, a humiliating tax for being a Christian, or be forcibly converted to Islam. Three months ago Saif Isam Shamer (aged 19) was shot dead for refusing to convert.
On June 3rd a minister and three deacons were shot dead as they dove away from their church in Mosul.
Dr Rebekka Zakaria, Mrs Ratna Bangun and Mrs Eti Pangesti are currently serving 3 years jail sentences for allowing Muslim children to attend a Christian club that they ran in Indonesia.
Walter Fazal Khan a 79 year old Pakistani Christian has been arrested having been falsely accused by his Muslim nephew who covets his property of setting fire to a Qur'an.
Sumaira Rafiq Masih, a Pakistani Christian aged 14, has been gang raped by three influential Muslim landowners near Patoki. No action has been taken by the authorities.
Shamimu Muteteri Hassan 9aged 16) was murdered by her father on July 1st in western Uganda for converting from Islam to Christianity.
David Shestakov is imprisoned in a labor camp in Uzbekistan for 'incitement to religious hatred'. He had been preaching Christ and him crucified.
Please pray for Christians suffering under Islam
On June 3rd a minister and three deacons were shot dead as they dove away from their church in Mosul.
Dr Rebekka Zakaria, Mrs Ratna Bangun and Mrs Eti Pangesti are currently serving 3 years jail sentences for allowing Muslim children to attend a Christian club that they ran in Indonesia.
Walter Fazal Khan a 79 year old Pakistani Christian has been arrested having been falsely accused by his Muslim nephew who covets his property of setting fire to a Qur'an.
Sumaira Rafiq Masih, a Pakistani Christian aged 14, has been gang raped by three influential Muslim landowners near Patoki. No action has been taken by the authorities.
Shamimu Muteteri Hassan 9aged 16) was murdered by her father on July 1st in western Uganda for converting from Islam to Christianity.
David Shestakov is imprisoned in a labor camp in Uzbekistan for 'incitement to religious hatred'. He had been preaching Christ and him crucified.
Please pray for Christians suffering under Islam
August News
Newsweek has this.
China has banned Buddhist monks in Tibet from reincarnating without government permission. According to a statement issued by the State Administration for Religious Affairs, the law, which goes into effect next month and strictly stipulates the procedures by which one is to reincarnate, is "an important move to institutionalize management of reincarnation."
It is August.
China has banned Buddhist monks in Tibet from reincarnating without government permission. According to a statement issued by the State Administration for Religious Affairs, the law, which goes into effect next month and strictly stipulates the procedures by which one is to reincarnate, is "an important move to institutionalize management of reincarnation."
It is August.
Thursday, August 23, 2007
How many mutations are you allowed?
Legend of figure.
Figure 1. Comparison of survival in months of patients with CLL with different degrees of sequence homology for IgVH genes.
For both panels. represents < 97% homology, between 97% and 97.9%,
between 98% and 99.9% and 100%.
Panel A shows overall survival censored for deaths unrelated to CLL; panel B shows treatment-free survival.
Summary
The choice of 98% sequence homology for immunoglobulin heavy chains to distinguish between mutated and unmutated versions of chronic lymphocytic leukaemia (CLL) was arbitrary and was chose to account for supposed polymorphisms. Some authors chose 97% or even 95%. In this study we have examined survival curves for cohorts of patients with varying degrees of sequence homology. All patients with <97% homology behaved as if mutated. Those with 97-98% homology were more aggressive than the mutated cases, but less aggressive than those with >98% homology.
Introduction
Although the difference between chronic lymphocytic leukemia (CLL) with mutated and unmutated immunoglobulin variable region heavy chain (IgVH) genes is well established and this distinction is recognised as one of the most important prognostic variables (Damle et al 1999; Hamblin et al 1999), the choice of 98% sequence homology as the limit of the unmutated subset was arbitrary, based on possible polymorphisms that might produce that degree of variation (Matsuda et al, 1993). Some authors chose 97% (Krober et al, 2002) or even 95% (Lin et al, 2002) homology as a possibly more appropriate cut-off. When a comparison was made of IgVH gene homology in leukaemic cells and granulocytes from the same patient, it became apparent that even small numbers of mutations were caused by somatic hypermutation rather than polymorphisms (Davis et al 2003).
Individuals whose IgVH genes have only a few somatic mutations comprise a small proportion of CLL patients and until recently it has not been possible to study enough patients in this group to distinguish a different prognostic impact of choosing the threshold for unmutated status at >97% or >98% homology. The problem is further complicated by the fact this is an elderly population in which many deaths are unrelated to CLL, and this adds ‘noise’ to the system making small differences difficult to perceive. A final difficulty is the discovery that the use of the VH3-21 gene is associated with a poor prognosis whether of not there are somatic mutations (Tobin et al 2002). This is especially problematic because such cases frequently have between 96 and 99% sequence homology.
In order to resolve these difficulties we have made a retrospective survey of 310 patients with CLL who have passed through our hands in the past 30 years and who have had their IgVH genes sequenced. We have compared outcomes of patients with different degrees of sequence homology. There were only four whose tumor used the VH3-21 gene, none of which fell in the disputed area of 97-98% homology; two had 100% and two <97% sequence homology. Patients were observed until treatment was indicated because of symptoms or evidence of progression, and then treated according to best practice of the day; largely with chlorambucil prior to 1990 and increasingly with purine analogues or combinations including purine analogues since then.
Methods.
310 patients with CLL were studied. Of these 260 were local patients representing the normal referral pattern of a district hospital and 50 were patients referred from other hospitals for a second opinion. The diagnosis was based on standard morphological and immunophenotypic criteria. Local patients were followed closely by the authors; data on referred patients were assembled from the referring physician by letter or telephone call. In the cases of patients who have died, an assessment of whether or not the cause of death was related to the CLL was made independently by two of the authors (TJH and DGO) and any discrepancy resolved by discussion. Except in cases with bone marrow suppression, deaths from cardiac or cerebral events were regarded as unrelated to CLL unless an infective episode or thrombocytopenia was involved. Deaths from cancer were regarded as unrelated unless there was an obvious relationship to the CLL.
IgVH gene analysis
Prior to October 2004 IgVH genes were originally sequenced as previously described (Hamblin et al, 1999)1. The preferred source material was RNA. cDNA was synthesized and amplified by polymerase chain reaction (PCR) using a mixture of oligonucleotide 5’ primers specific for each leader sequence of the VH1 to VH6 families or a consensus 5’ FW1 region primer, together with either a consensus 3’ primer complementary to the germ line JH regions or a 3’ primer complimentary to the constant region. From 2004 onwards gDNA was extracted from whole blood using the QIAmp®DNA mini kits (Qiagen, Crawley, West Sussex, UK) according to the manufacturers instructions. gDNA was amplified in a single multiplexed PCR reaction consisting of 6VH framework 1 primers combined with one JH consensus primer (standardises BIOMED-2 primers) (van Dongen et al, 2003; Matthews et al, 2004). Clonal sequences were determined by sequencing amplicons from at least 2 independent PCR reactions. The majority of samples were sequenced directly using an automated DNA sequencer. Nucleotide sequences were aligned to EMBL/GenBank and current databases (V-BASE sequence directory IMGT/V-QUEST, using MacVector 4.0 sequence analysis software; International Biotecnologies, New Haven, CT, and Lasegene; DNASTAR, Madison, WI.). Percentage homology was calculated by counting the number of mutations between the 5’ end of FR1 and the 3’ end of FR3.
Statistical methods
Data were analysed using GraphPad Prism 4. Survival functions comparing patients have been estimated using the product limit method of Kaplan Meier.
Results
There were 99 patients with 100% sequence homology, 22 with between 98 and 99.9%, 22 with between 97 and 97.9%, 24 with between 96 and 96.9%, and 143 with <96% homology with germ line genes. There have been 139 deaths of which 79 were determined to be unrelated to CLL. Survival curves are shown in figure 1. The median survivals, censored for unrelated deaths, were 102 months for patients with 100% IgVH gene homology; 132 months for those with 98-99.9%, 184 months for those with 97-97.9% and not yet reached for those with 96% or <96%. The difference between 100% and 97-97.9% was statistically significant (p=0.002) as was the difference between 97-97.9% and <97% (p<0.0001). However, the differences between 100% and 98-99.9% and between 98-99.9% and 97-97.9% did not reach statistical significance. The survival curves for those with 96-96.9% homology and <96% were virtually identical.
Using treatment-free survival as an alternative end-point gave very similar results. Median times to treatment were 35 months for 100% homology, 36 months for 98-99.9%, 156 months for 97-97.9%, and 272 months for <97%. The difference between 100% and 97-97.9% was statistically significant (p=0.001) as was the difference between 97-97.9% and <97% (p=0.0003), but the differences between 100% and 98-99.9%, between 98-99.9% and 97-97.9%, and between 96-96.9% and <96% were not.
Discussion
The pattern revealed by this study is not a continuous gradation with survival increasing with increases in the number of mutations. Those with 97%-97.9% homology comprise a mixture of benign and malignant cases rather than a homogeneous group with moderate malignancy.
It is not understood how accumulations of somatic mutations affects prognosis in CLL. The initial explanation, that in those with mutated IgVH genes the cells had passed through the germinal centre while the cells of those with unmutated IgVH genes had not, seems unlikely to be true. Tumour cells from both types of patients most closely resemble memory B cells (Klein et al, 2001) and both express CD27 (Dong et al, 2002). Furthermore, among both mutated and unmutated CLLs there are now many examples of non-stochastic pairing of immunoglobulin heavy and light chains predicated by the sequences of the CDR3 of the Ig heavy chain, combining to form stereotypic antibody-combining-sites indicative of selection by as yet unknown extrinsic or self antigens (Widhopf et al, 2007). All these facts point to the clear conclusion that both types of CLL should be thought of as derived from antigen-experienced B cells.
Poor prognosis in patients with unmutated IgVH genes is particularly associated with those who acquire other poor prognostic factors such as CD38 (Hamblin et al, 2002), ZAP-70 (Rassenti et al, 2004) and chromosomal deletions at 11q23 and 17p13 (Dohner et al, 2000). It is not known why these abnormalities are preferentially acquired in patients with unmutated IgVH genes, nor whether those with between 97% and 97.9% homology are among those that preferentially acquire them.
One possible mechanism is that the mutator mechanism is impaired in CLLs with unmutated IgVH genes. The anomalously high expression of activation-induced cytosine deaminase (AID), an enzyme necessary for somatic hypermutation and Ig class switching, in cases with unmutated IgVH genes (Albesiano et al 2003; McCarthy et al 2003; Oppezzo et al, 2003) may be implicated. It has been suggested that high levels of AID may result in loss of substrate specificity and the development of mutations in c-MYC, PAX-5 and RhoH genes which are associated with more aggressive forms of the disease (Reiniger et al, 2006). It would be interesting to see whether the level of AID correlates with the degree of somatic hypermutation and whether this is a factor in the acquisition of other poor prognostic factors.
References
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