Several people have asked whether having a paraprotein in the serum influences the outcome in CLL. A paper in Leukemia Research from China addresses this problem.
They studied 133 patients with CLL, 86 male and 47 female, median age at diagnosis 60 (range, 44–84). They identified 27 patients with Ig paraproteinemia (12 with IgG, 12 with IgM, 3 with both IgG and IgM, but none with IgA), frequency of 20.3%. The median level of serum IgG paraprotein was 28.2 g/l (range, 21.0–62.0 g/l), and IgM paraprotein was 18.1 g/l (range, 2.3–49.1 g/l). The serum monoclonal Ig light chain concordant with the monoclonal Ig light chain expressed by the neoplastic cells in all patients with Ig paraproteinemia.
Strong correlations of serum Ig paraprotein with advanced Binet stage, DAT-positivity, high level of Beta2-MG and TK1, absence of IGHV mutations, ZAP-70-positivity, CD38-positivity, and cytogenetic abnormalities of del(17p13) or del(11q22)were observed.
With a median follow-up of 36 months (range, 4–83 months), 13 patients (9.8%) died. The prognostic factors with statistical significance were considered in a multivariate Cox regression analysis, del(17p13) ZAP-70, and IgM paraproteinemia were the variables strongly associated with survival.
Ig paraproteinemia was associated with poor outcome. Six (22.2%) with Ig paraproteinemia died during the observation period (2 with IgG paraprotein, 2 with IgM paraprotein, 2 patients with both IgG and IgM, respectively), whereas among the 106 patients without Ig paraproteinemia, 7 (6.6%) died. Patients with Ig paraproteinemia had significantly shorter survival times than patients without serum Ig paraprotein.
Bernstein and colleagues], in a study of 111 patients, reported that the presence of serum monoclonal protein in patients with CLL was associated with a shorter median
survival: 63 months for patients with CLL with serum Ig paraprotein compared with 103 months for patients without serum Ig paraprotein. However, Yin and colleagues have not confirmed this observation. The unfavorable prognostic significance of serum Ig paraprotein was observed in this study.
The possible explanations of discrepancy in prognostic impact of serum Ig paraprotein might be different therapeutic regimens, shorter clinical follow-up and smaller number of patients. retained their capability of isotype switching, a process independent of immunoglobulin heavy chain gene mutation. As an alternative, these additional M components may represent biclonal or triclonal ymphoproliferative disorders as described in the literature or the development of a subclone within the original tumor cells due to clonal evolution.
For myself I'm not sure there is anything in this. Perhaps the Chinese population is strange, but this seems a very high incidence of a paraprotein in CLL, which we found at only about 2%. I wonder if in China there is a lymphoplasmacytoid lymphoma that closely resembles CLL.
Wednesday, July 20, 2011
Signaling in CLL: opportunities for treatment
Can anything be done at this stage of signaling to block it like Gleevec blocks bcr/abl? Two selective Lyn inhibitors, PP2 and SU6656, block Lyn kinase activity and induce apoptosis, but I know of no trials of these in clinical practice.
Elevated Syk expression by CLL cells results in activation of its downstream targets including Plc2, Erk and Akt. Selective Syk inhibitors BAY-61-3606 and R406 induce apoptosis of CLL cells. siRNA knockdown suggested that constitutively-active Syk maintains high levels of antiapoptotic Mcl-1 via protein kinase C (PKC) δ, which blocks proteasomal degradation of Mcl-1. Downregulation of Mcl-1 in CLL cells treated with Syk inhibitors is consistent with this hypothesis. The susceptibility of CLL cells to apoptosis induction by Syk inhibitors correlated with levels of Syk expression.
In other words Syk signal increase Mcl-1 levels and this seems to be the major agent that stops CLL cells dying. Syk inhibitors might well be effective in treating CLL.
Syk has also been implicated in signalling by chemokines and by integrins. Syk inhibition by R406 or siRNA-mediated knockdown of this PTK abrogated the protective effects of these signals.
Fostamatinib disodium (R788), an orally bioavailable prodrug of R406, blocked BCR signalling in vivo in malignant cells of the Eμ-TCL1 mouse model of CLL, decreased proliferation and survival of malignant cells and prolonged survival of the animals. The drug did not affect the generation of normal B cells. Six of eleven CLL patients treated with fostamatinib showed objective responses in one small clinical trial.
So Fostamatinib shows early promise in treatment. Perhaps in combination with other agents it might be useful.
Imatinib and dasatinib are selective inhibitors of the Abl PTK. Abl expression levels correlated positively with tumour burden and negatively with IGHV mutation levels. Imatinib induced apoptosis of CLL cells that express high levels of Abl. Dasatinib also induced CLL apoptosis in vitro. Dasatinib is a dual inhibitor of Abl and Src PTKs and its critical target with respect to apoptosis induction in CLL cells is not clear at present.
Comment: I think I have already written about Gleevec in CLL.
Elevated Syk expression by CLL cells results in activation of its downstream targets including Plc2, Erk and Akt. Selective Syk inhibitors BAY-61-3606 and R406 induce apoptosis of CLL cells. siRNA knockdown suggested that constitutively-active Syk maintains high levels of antiapoptotic Mcl-1 via protein kinase C (PKC) δ, which blocks proteasomal degradation of Mcl-1. Downregulation of Mcl-1 in CLL cells treated with Syk inhibitors is consistent with this hypothesis. The susceptibility of CLL cells to apoptosis induction by Syk inhibitors correlated with levels of Syk expression.
In other words Syk signal increase Mcl-1 levels and this seems to be the major agent that stops CLL cells dying. Syk inhibitors might well be effective in treating CLL.
Syk has also been implicated in signalling by chemokines and by integrins. Syk inhibition by R406 or siRNA-mediated knockdown of this PTK abrogated the protective effects of these signals.
Fostamatinib disodium (R788), an orally bioavailable prodrug of R406, blocked BCR signalling in vivo in malignant cells of the Eμ-TCL1 mouse model of CLL, decreased proliferation and survival of malignant cells and prolonged survival of the animals. The drug did not affect the generation of normal B cells. Six of eleven CLL patients treated with fostamatinib showed objective responses in one small clinical trial.
So Fostamatinib shows early promise in treatment. Perhaps in combination with other agents it might be useful.
Imatinib and dasatinib are selective inhibitors of the Abl PTK. Abl expression levels correlated positively with tumour burden and negatively with IGHV mutation levels. Imatinib induced apoptosis of CLL cells that express high levels of Abl. Dasatinib also induced CLL apoptosis in vitro. Dasatinib is a dual inhibitor of Abl and Src PTKs and its critical target with respect to apoptosis induction in CLL cells is not clear at present.
Comment: I think I have already written about Gleevec in CLL.
John Trapnell - a sinner saved by grace
I went to the celebration of John Trapnell's life yesterday at Ringwood Parish Church. Although I knew John very well and for a longer period than most of the 300+ in the congregation, there were things I did not know about him. For example, I had not appreciated how much he and I shared similar tastes in music and it would have been great to go to the opera with him. We did have a mutual friend in Peter Witham, who taught my son violin and for many years was my contact with the Bournemouth Symphony Orchestra who often performed for Tenovus, one of the charities that I ran. But John was also involved with the school choir at Ringwood after his retirement, which I knew nothing about.
John had offered in the past to take me sailing, but I was put off by my experience in a sailing dinghy when I was younger. It was a cold and wet endeavour. (Endeavour was the name of Captain James Cook's boat, I believe). John's boats were a little larger than sailing dinghies.
It was good to see some of my old colleagues at the celebration, though fewer than I had hoped. Mostly they were retired and many suffering from the way that old age bites into your life as it does into mine.
Something of John's personality came over. He had insisted to David Craig, his long-time friend and Pastor, that the 'warts' should not be hidden. They were not. John came from a privileged background and led a very blessed life, but there were adversities, some of which were of his own making. He claimed never to have thrown instruments in the Operating Room. He later amended that to saying he had never thrown them at anyone. He was certainly opinionated and some thought him arrogant. But h could be exceedingly humble and he was well aware of his faults. He prayed before every operation and was exceedingly kind to his patients, who genuinely loved him. Some of the things I knew about him are best not said, since they have been repented of and if the Lord can 'see them no more' I don't see why anyone else should.
He was certainly a 'sinner saved by grace' and for those who don't understand that let me explain. Grace is not just a Girl's name, nor something to do with graceful. It has a specific Christian meaning of the unmerited and freely given forgiveness and mercy of God. After I was first converted, my new Pastor, Harry Kilbride, took me for a long walk and taught me the Doctrines of Grace. I have stuck to them ever since.
The Grace doctrines are often described by the acronym TULIP. The T stands for Total depravity. This does not mean that all humans are totally depraved. It sounds really wild in today's world and probably, as words change their meaning, ought to be modified. What it does mean is that every man and woman, every child and baby, has been corrupted by the Fall, and corrupted in every part of their being. It was certainly the case that Adam and Eve were perfect when they were created, but by their wilful disobedience to God, they caused the world and everything in to be cursed. This is known theologically as the Fall. Importantly, it means that every part of Man is corrupted including his will. Of course we are not as bad as we possibly could be. There is still some semblance of what God saw when he pronounced His creation 'good', but it has been marred in every part. Especially this is true about the will. It means that we could not choose to love God with all our heart mind and strength, because our will is corrupt. That choice is not available to us; we will always choose self over God.
That does not prevent us doing good things; atheists may do splendid things, but it stops us from choosing the best. Lutherans tend to believe the same thing on this, but many Methodists were say that their will is free to choose Christ.
The 'U' stands for Unconditional election. This means that God has chosen to save some without regard to whether they were good or bad; without even foreseeing or predestining that they would be come good. It was just an act of love of unmerited mercy. He loved us because he loved us.
There is a danger in this that we should think of ourselves as special, as the chosen people. That is why it must be stressed that this is unmerited. He chose us before the creation of the world because if he had waited to see what we were like he would certainly have discarded us. This is why churches are like hospitals, full of sick people. Never look for perfect Christians in a church; you are sure to be disappointed. An unfortunate correlation with election is that those who are not chosen are condemned. It sounds like God has elected some for damnation - the Lutherans leave this part out completely. But it is open to Man to choose God without His help; it's just that he never does.
The 'L' stands for Limited atonement. Atonement is one of those technical words that mean nothing to most people these days, but it is quite simple. The word means at one ment. It means that we and God are at one with each other. Before, God was angry with the human race because of our disobedience to him. But God had provide the means of assuaging that anger, his son taking the penalty of sin for us on the cross. Many other branches of Christianity believe that the atonememnt was for everybody, but the doctrines of grace suggest it was while potentially sufficient for everybody, in effect it was limited to the elect.
The 'I' stands for Irresistible grace; Lutherans believe it is resistible and Methodists synergistic.
The 'P' stands for the preservation of the saints. It means that once you are saved you cannot be unsaved. Of course some fall away, but they were never saved in the first place - they just gave the appearance of salvation. Lutherans believe that falling away of the saints through apostasy is possible and Methodists that preservation of the saints is conditional on holding on to faith. Some Calvinists are 4 or 4.5 pointers and are less strong on some of these doctrinal points. Among the more famous Calvinists are Jim Packer, Tim Keller and John Piper.
John Trapnell was a five pointer and had good reason to be. Without such grace he could never have been saved.
John had offered in the past to take me sailing, but I was put off by my experience in a sailing dinghy when I was younger. It was a cold and wet endeavour. (Endeavour was the name of Captain James Cook's boat, I believe). John's boats were a little larger than sailing dinghies.
It was good to see some of my old colleagues at the celebration, though fewer than I had hoped. Mostly they were retired and many suffering from the way that old age bites into your life as it does into mine.
Something of John's personality came over. He had insisted to David Craig, his long-time friend and Pastor, that the 'warts' should not be hidden. They were not. John came from a privileged background and led a very blessed life, but there were adversities, some of which were of his own making. He claimed never to have thrown instruments in the Operating Room. He later amended that to saying he had never thrown them at anyone. He was certainly opinionated and some thought him arrogant. But h could be exceedingly humble and he was well aware of his faults. He prayed before every operation and was exceedingly kind to his patients, who genuinely loved him. Some of the things I knew about him are best not said, since they have been repented of and if the Lord can 'see them no more' I don't see why anyone else should.
He was certainly a 'sinner saved by grace' and for those who don't understand that let me explain. Grace is not just a Girl's name, nor something to do with graceful. It has a specific Christian meaning of the unmerited and freely given forgiveness and mercy of God. After I was first converted, my new Pastor, Harry Kilbride, took me for a long walk and taught me the Doctrines of Grace. I have stuck to them ever since.
The Grace doctrines are often described by the acronym TULIP. The T stands for Total depravity. This does not mean that all humans are totally depraved. It sounds really wild in today's world and probably, as words change their meaning, ought to be modified. What it does mean is that every man and woman, every child and baby, has been corrupted by the Fall, and corrupted in every part of their being. It was certainly the case that Adam and Eve were perfect when they were created, but by their wilful disobedience to God, they caused the world and everything in to be cursed. This is known theologically as the Fall. Importantly, it means that every part of Man is corrupted including his will. Of course we are not as bad as we possibly could be. There is still some semblance of what God saw when he pronounced His creation 'good', but it has been marred in every part. Especially this is true about the will. It means that we could not choose to love God with all our heart mind and strength, because our will is corrupt. That choice is not available to us; we will always choose self over God.
That does not prevent us doing good things; atheists may do splendid things, but it stops us from choosing the best. Lutherans tend to believe the same thing on this, but many Methodists were say that their will is free to choose Christ.
The 'U' stands for Unconditional election. This means that God has chosen to save some without regard to whether they were good or bad; without even foreseeing or predestining that they would be come good. It was just an act of love of unmerited mercy. He loved us because he loved us.
There is a danger in this that we should think of ourselves as special, as the chosen people. That is why it must be stressed that this is unmerited. He chose us before the creation of the world because if he had waited to see what we were like he would certainly have discarded us. This is why churches are like hospitals, full of sick people. Never look for perfect Christians in a church; you are sure to be disappointed. An unfortunate correlation with election is that those who are not chosen are condemned. It sounds like God has elected some for damnation - the Lutherans leave this part out completely. But it is open to Man to choose God without His help; it's just that he never does.
The 'L' stands for Limited atonement. Atonement is one of those technical words that mean nothing to most people these days, but it is quite simple. The word means at one ment. It means that we and God are at one with each other. Before, God was angry with the human race because of our disobedience to him. But God had provide the means of assuaging that anger, his son taking the penalty of sin for us on the cross. Many other branches of Christianity believe that the atonememnt was for everybody, but the doctrines of grace suggest it was while potentially sufficient for everybody, in effect it was limited to the elect.
The 'I' stands for Irresistible grace; Lutherans believe it is resistible and Methodists synergistic.
The 'P' stands for the preservation of the saints. It means that once you are saved you cannot be unsaved. Of course some fall away, but they were never saved in the first place - they just gave the appearance of salvation. Lutherans believe that falling away of the saints through apostasy is possible and Methodists that preservation of the saints is conditional on holding on to faith. Some Calvinists are 4 or 4.5 pointers and are less strong on some of these doctrinal points. Among the more famous Calvinists are Jim Packer, Tim Keller and John Piper.
John Trapnell was a five pointer and had good reason to be. Without such grace he could never have been saved.
Stem cell successes
In the past week we have heard of two stem cell successes. In one a man was transplanted with a new trachea (windpipe). A 36-year-old man whose own cancerous trachea had to be removed was treated with the procedure on 9 June at the Karolinska University Hospital in Stockholm, Sweden, by Paolo Macchiarini.
No donor was needed for the new procedure. Instead the tissue was custom-built to fit the patient, then coated inside and out with his own stem cells. The treatment began after Alexander Seifalian of University College London received detailed scans of the patient's diseased trachea. Using these, Seifalian constructed a bespoke replacement from a novel polymeric material that he has developed and patented.
Two days before the operation, the team took 200 ml of bone marrow from the patient and from this extracted 40 ml of mesenchymal stem cells. By pouring these on top of the synthetic organ in a bioreactor developed by Harvard Bioscience of Holliston, Massachusetts, the trachea was successfully coated inside and out with the patient's own cells.
During surgery, Macchiarini's final touch was to add patches of the patient's nose lining to the inner surface of the trachea. These later grew into a layer of epithelial cells matching those lining the inner surfaces of the respiratory tract.
"The big conceptual breakthrough is that we can move from transplanting organs to manufacturing them,” says David Green, the president of Harvard Bioscience – although he adds that the concept would work best for simple structures such as tracheas, ureters and blood vessels.
In another stem cell development, a company called FCB-Pharmicell based in Seongnam, South Korea, became the first in the world to receive official approval for a stem-cell-based procedure to treat people who have survived heart attacks. In the newly approved procedure, stem cells are extracted from the patient's bone marrow, multiplied in the lab then injected directly into the heart through the coronary artery.
Little clinical data is publicly available to prove that the procedure benefits patients, but according to press reports last week, the company says that in trials, patients showed 6 per cent improvements in heart function six months after the procedure, compared with untreated patients.
It is important to recognize that these reports do not derive from embryonic stem cells which have to be produced from spare embryos manufactured by IVF, but from mesenchymal stem cells which come from the patient's own tissue (often bone marrow) that carries neither ethical not rejection risk.
No donor was needed for the new procedure. Instead the tissue was custom-built to fit the patient, then coated inside and out with his own stem cells. The treatment began after Alexander Seifalian of University College London received detailed scans of the patient's diseased trachea. Using these, Seifalian constructed a bespoke replacement from a novel polymeric material that he has developed and patented.
Two days before the operation, the team took 200 ml of bone marrow from the patient and from this extracted 40 ml of mesenchymal stem cells. By pouring these on top of the synthetic organ in a bioreactor developed by Harvard Bioscience of Holliston, Massachusetts, the trachea was successfully coated inside and out with the patient's own cells.
During surgery, Macchiarini's final touch was to add patches of the patient's nose lining to the inner surface of the trachea. These later grew into a layer of epithelial cells matching those lining the inner surfaces of the respiratory tract.
"The big conceptual breakthrough is that we can move from transplanting organs to manufacturing them,” says David Green, the president of Harvard Bioscience – although he adds that the concept would work best for simple structures such as tracheas, ureters and blood vessels.
In another stem cell development, a company called FCB-Pharmicell based in Seongnam, South Korea, became the first in the world to receive official approval for a stem-cell-based procedure to treat people who have survived heart attacks. In the newly approved procedure, stem cells are extracted from the patient's bone marrow, multiplied in the lab then injected directly into the heart through the coronary artery.
Little clinical data is publicly available to prove that the procedure benefits patients, but according to press reports last week, the company says that in trials, patients showed 6 per cent improvements in heart function six months after the procedure, compared with untreated patients.
It is important to recognize that these reports do not derive from embryonic stem cells which have to be produced from spare embryos manufactured by IVF, but from mesenchymal stem cells which come from the patient's own tissue (often bone marrow) that carries neither ethical not rejection risk.
John 5:43. Anyone but Jesus
I have come in my Father’s name, and you do not accept me; but if someone else comes in his own name, you will accept him.
In fact, the Jews followed after several Messianic pretenders. It was a case of anyone but Jesus. They refused to accept anyone preaching the gospel of the suffering servant. Such was their arrogance, they did not see that they were sinners in need of repentance. We are the chosen people. The doctrines of grace are paramount in Christian theology. Followers of Jesus need to recognize their own abject inadequacy and their total dependence on Jesus
In fact, the Jews followed after several Messianic pretenders. It was a case of anyone but Jesus. They refused to accept anyone preaching the gospel of the suffering servant. Such was their arrogance, they did not see that they were sinners in need of repentance. We are the chosen people. The doctrines of grace are paramount in Christian theology. Followers of Jesus need to recognize their own abject inadequacy and their total dependence on Jesus
Tuesday, July 19, 2011
Hizb ut-Tahrir
Our last three Prime Ministers have all wanted to ban the Islamist Group Hizb-ut-Tahrir, but all have failed to do so. Why?
The reason seems to be that current legislation allows the banning of groups that act violently and those that foment violence. Hizb-ut-Tahrir, it seems just have unpleasant views and you can't be banned for those.
This is probably a good thing; otherwise we would be ruled by the thought police. Lord Carlile, the previous counter-terrorism reviewer, said yesterday, "I don't think anything is going to happen … I think the general view is that Hizb ut-Tahrir are best dealt with in public debate rather than by proscription."
They seem to be being defeated in public debate. They had their annual conference in Tower Hamlets recently and the turnout was 200 people, down from several thousand four years ago. This is a group that is rushing towards extinction
The reason seems to be that current legislation allows the banning of groups that act violently and those that foment violence. Hizb-ut-Tahrir, it seems just have unpleasant views and you can't be banned for those.
This is probably a good thing; otherwise we would be ruled by the thought police. Lord Carlile, the previous counter-terrorism reviewer, said yesterday, "I don't think anything is going to happen … I think the general view is that Hizb ut-Tahrir are best dealt with in public debate rather than by proscription."
They seem to be being defeated in public debate. They had their annual conference in Tower Hamlets recently and the turnout was 200 people, down from several thousand four years ago. This is a group that is rushing towards extinction
John 5:41-42. Man-pleasing.
I do not accept praise from men, but I know you do not have the love of God in your hearts.
Most men love the praise of others, but Jesus was only concerned with the praise of God the Father who sent him.
We love to look well in the eyes of other people, but this gets in the way of our love for God and our appreciation of His love for us. What commends us to men? Our wealth? Our cleverness? Our wit? Would that it were our honesty, our humility, or our sacrifice.
Even those who lead us are tempted lest their performance in the pulpit is insufficient or their prayer-life inadequate or their preparation of sermons underdone. It is good to do our best for the Lord, but man-pleasing is not what we are here for.
For those with the love of God in their hearts it is only God they seek to please. Imagine a man besotted with his new wife. Should he treat her in such a way that impresses the neighbors? In no way! His job is to please his new wife.
Most men love the praise of others, but Jesus was only concerned with the praise of God the Father who sent him.
We love to look well in the eyes of other people, but this gets in the way of our love for God and our appreciation of His love for us. What commends us to men? Our wealth? Our cleverness? Our wit? Would that it were our honesty, our humility, or our sacrifice.
Even those who lead us are tempted lest their performance in the pulpit is insufficient or their prayer-life inadequate or their preparation of sermons underdone. It is good to do our best for the Lord, but man-pleasing is not what we are here for.
For those with the love of God in their hearts it is only God they seek to please. Imagine a man besotted with his new wife. Should he treat her in such a way that impresses the neighbors? In no way! His job is to please his new wife.
Signaling in CLL 2
Zap-70 is the PTK that signals in T cells. Although high Zap-70 expression correlates with poor prognosis in CLL, the precise role of this PTK in CLL is not clear.
In Zap-70-positive CLL cells, it becomes tyrosine phosphorylated and associated with CD79b following BCR engagement and indeed tyrosine phosphorylation of Syk is greater than in Zap-70-negative cells. If you transduce Zap-70 into CLL cells there is enhanced BCR signalling, but this is independent of the PTK activity of Zap-70. Zap-70 may therefore function either as an adaptor protein that augments Syk activation or as a decoy that sequesters a negative regulator of Syk.
Zap-70 may contribute to drug resistance by enhancing migratory responses of CLL cells to the chemokines CCL 19 and 21, thus promoting migration of malignant cells to sites where apoptosis resistance is enhanced by microenvironmental signalling.
The RhoH guanine nucleotide-binding protein contains ITAM motifs and is an adaptor that recruits Zap-70 to T lymphocyte antigen receptors. RhoH is overexpressed in CLL cells relative to normal B cells. Deletion of RhoH retards progression of the CLL-like disease of Eμ-TCL-1 transgenic mice, implying that overexpression of RhoH contributes to CLL pathology by augmenting the contribution of Zap-70 to antigen receptor signalling.
In lay language: Although ZAP-70 positive CLL cells are more malignant, ZAP-70 does not take part in the active signaling process in CLL, the way it does in T-cells. It may act either as an enhancer of Syk activation or as a suprressor of Syk inhibition. It also may act by increasing the response of CLL cells to chemokines, so pushing them into parts of the microenvironment where there are other factors producing resistance to apoptosis.
RhoH is another signaling protein that is important in T cells that is increased in CLL cells. In the TCL-1 animal model for CLL, the disease is retarded if RhoH is deleted, which implies it might have an active role in CLL like that of Zap-70.
In Zap-70-positive CLL cells, it becomes tyrosine phosphorylated and associated with CD79b following BCR engagement and indeed tyrosine phosphorylation of Syk is greater than in Zap-70-negative cells. If you transduce Zap-70 into CLL cells there is enhanced BCR signalling, but this is independent of the PTK activity of Zap-70. Zap-70 may therefore function either as an adaptor protein that augments Syk activation or as a decoy that sequesters a negative regulator of Syk.
Zap-70 may contribute to drug resistance by enhancing migratory responses of CLL cells to the chemokines CCL 19 and 21, thus promoting migration of malignant cells to sites where apoptosis resistance is enhanced by microenvironmental signalling.
The RhoH guanine nucleotide-binding protein contains ITAM motifs and is an adaptor that recruits Zap-70 to T lymphocyte antigen receptors. RhoH is overexpressed in CLL cells relative to normal B cells. Deletion of RhoH retards progression of the CLL-like disease of Eμ-TCL-1 transgenic mice, implying that overexpression of RhoH contributes to CLL pathology by augmenting the contribution of Zap-70 to antigen receptor signalling.
In lay language: Although ZAP-70 positive CLL cells are more malignant, ZAP-70 does not take part in the active signaling process in CLL, the way it does in T-cells. It may act either as an enhancer of Syk activation or as a suprressor of Syk inhibition. It also may act by increasing the response of CLL cells to chemokines, so pushing them into parts of the microenvironment where there are other factors producing resistance to apoptosis.
RhoH is another signaling protein that is important in T cells that is increased in CLL cells. In the TCL-1 animal model for CLL, the disease is retarded if RhoH is deleted, which implies it might have an active role in CLL like that of Zap-70.
Monday, July 18, 2011
Understanding cell signaling
My old friend Stan Wickremasinghe has written a beautiful review of signalling in Brit J Haem and I intend to use it as a teaching tool on this blog. This will be a series of blogs because my experience is that I can only really take in about one fact at a time and since this isn't really my field, I shall be learning too.
The B-cell receptor (BCR) is the B-cells gateway to the outside world. It is in fact an antibody molecule, designed to recognize the antigen that the B-cell is programmed to react with. But it does not connect to anything inside the cell. For this it has to interact with the Ig associated molecules CD79a and CD79b.
When the BCR transmembrane immunoglobulin molecule is engaged by antigen the CD79 a and b proteins of the BCR, the Protein Tyrosine Kinase (PTK), Lyn, is activated. Phosphorylation of tyrosine residues within an immune receptor tyrosine-based activation motif (ITAM) sequence in the C-terminal tail of the CD79 molecules results in recruitment of an additional PTK, Syk, resulting in generation of further phosphotyrosine sites. Binding of the SH2-containing protein phosphatase 1 (Shp1) to immune receptor tyrosine-based inhibitor motifs (ITIMs) on transmembrane molecules (including CD22) results in dephosphorylation of phosphotyrosines, providing negative regulation of BCR signalling.
In plain English, in a B-cell, the immunoglobulin molecule on the surface binds to the antigen it was designed for - eg an anti-measles antibody binds to a measles virus. But a CLL cell is probably only rarely designed to fight measles - it looks like the target for CLL cells are proteins released from dying cells in many cases. The immunoglobulin molecule needs an auxiliary molecule to help it signal - this is CD79 (often low in CLL, so is this why it often does not signal very well?)
Activation of CD79 alerts two tyrosine kinases, Lyn and Syk, which are capable of sending messages onward through the cell. Lyn, at least, is thought to act like a rheostat, controling the strength of signal that is sent onwards. It seems to do this by invoking a suppressing signal, binding to the inhibitory protein Shp1 on CD22, which is normally present on B-cells in association with the BCR. (But surface CD22 on CLL cells is either absent or very reduced. It can be detected intracellularly though. Is there more to learn here?)
Family matters
The newspapers are full of the phone hacking fiasco and the public is bored by it. Newspapers think that their little world is important but nobody else does.
Let's talk about cricket instead. My son's team played in the 20/20 final of the South Northamptonshire cricket league. In a low scoring match on a rain affected pitch his team was all out for 82 of which he scored 22. Then the opposition were bowled out for 61 of which he took 4-17 in 4.2 overs. He got man-of-match, cut the grass and made the tea.
His team are top of division 5 and with only 5 more games before the end of the season look like being promoted.
He is off in Italy at the present preparing for the NASCAR series. It's a nice life if you don't weaken.
Today Karen returns from her holiday in Jamaica and Angela starts hers in the Lake District. Contrasting weather! Angela has taken her lap-top so I imagine that she will be writing up her PhD is the weather sets in.
Richard will be in the Isle of Wight when the school holidays begin.
We had a new front lawn laid over the weekend and today. Good weather for lawn laying - cool and wet.
Health has not been special these last few days. I'm very tired after meals and bloating has got worse.
Let's talk about cricket instead. My son's team played in the 20/20 final of the South Northamptonshire cricket league. In a low scoring match on a rain affected pitch his team was all out for 82 of which he scored 22. Then the opposition were bowled out for 61 of which he took 4-17 in 4.2 overs. He got man-of-match, cut the grass and made the tea.
His team are top of division 5 and with only 5 more games before the end of the season look like being promoted.
He is off in Italy at the present preparing for the NASCAR series. It's a nice life if you don't weaken.
Today Karen returns from her holiday in Jamaica and Angela starts hers in the Lake District. Contrasting weather! Angela has taken her lap-top so I imagine that she will be writing up her PhD is the weather sets in.
Richard will be in the Isle of Wight when the school holidays begin.
We had a new front lawn laid over the weekend and today. Good weather for lawn laying - cool and wet.
Health has not been special these last few days. I'm very tired after meals and bloating has got worse.
John 5:39-40. Blind to Scripture
You diligently study the Scriptures because you think by them you possess eternal life. These are the Scriptures that testify about me yet you refuse to come to me to have life.
As evangelicals we set great store by the Scripture. We believe that every word is 'God-breathed'. We admit to no changes to what was originally given. We believe them to be historically true, even when the whole of modern science is set against some of them.
The Pharisees too set great store by the Scripture. When the Scribes were copying them they assigned a number to each letter and added up each row and column as a guard against error creeping in. But of more importance than the book is what it says. When Jesus opened up the Scriptures on the road to Emmaus is was clear that even his disciples didn't understand what the Old Testament was saying about him.
The Pharisees were more fortunate than we; they didn't just have the Scripture; they had Jesus. You see you need the Holy Spirit's eyes to read the Word of God.
As evangelicals we set great store by the Scripture. We believe that every word is 'God-breathed'. We admit to no changes to what was originally given. We believe them to be historically true, even when the whole of modern science is set against some of them.
The Pharisees too set great store by the Scripture. When the Scribes were copying them they assigned a number to each letter and added up each row and column as a guard against error creeping in. But of more importance than the book is what it says. When Jesus opened up the Scriptures on the road to Emmaus is was clear that even his disciples didn't understand what the Old Testament was saying about him.
The Pharisees were more fortunate than we; they didn't just have the Scripture; they had Jesus. You see you need the Holy Spirit's eyes to read the Word of God.
FISH and Karytotype
We have come to rely on FISH to tell us about the chromosomes in CLL, but it is not a very satisfactory test. It will tell us about the abnormalities that we know exist in CLL - del 13q, del 11q, trisomy 12 and del 17p - but not about ones that we don't look for. In particular we know that isolated del 13q usually has a good prognosis, but unless we look at other chromosomes how do we know it is isolated.
The standard way of looking at chromosomes is to make cells divide, but in CLL this is very difficult. You need a mitogen and the standard mitogen is phorbol ester. Unfortunately although our lab gets over 80% of CLL cells to divide, nobocy else in the world can match our results. This has led other labs to experiment with cytokines to stimulate the CLL cells to divide.
In this month's Leukemia Research, a paper from Poland describes the use of a new mitogen, DSP30. DSP30 is a CpG-oligonucleotide (CpG-ODN). CpG-ODNs act as danger signals and stimulate the immune system. It induces proliferation
of both normal and leukemic B lymphocytes, stimulates production of cytokines, including IL-2 and TNF- , and regulates expression of surface antigens CD25 and CD86 in B lymphocytes. It also stimulates some other immune system cells, such as T lymphocytes, NK cells, dendritic cells and monocytes, to proliferate, secrete cytokines and/or differentiate.
Using DSP30, a sufficient number of metaphases suitable for analysis was obtained in 56/62 (90%) patients, and clonal chromosomal aberrations were detected in 42/56 (75%) patients. Normal karyotype was established in 14/56 (25%). In 9/14 (64%) cases with normal karyotype, aberrations were detected by FISH which revealed anomalies in 52/62 (84%) patients. Using DSP30 and/or FISH, aberrations were detected in 56/62
(90%) patients. DSP30 disclosed del 13q in only 10/56 (18%) cases, while FISH showed this anomaly in 41/62 (66%) subjects. Del 13q was cryptic and not detected by DSP30 in 28 patients. In those cases the presence of submicroscopic del 13q was confirmed by FISH on metaphases. In 4/41 (9.7%) patients del 13q were biallelic or concomitant monoallelic and biallelic. In 26/41 (63%) patients del 13q detected by FISH was a sole anomaly. Del 11q was detected by both FISH and DSP30 in 14 patients, whereas in two patients it was detected only by FISH due to an unsuccessful karyotyping. DSP30 enabled the detection of additional aberrations, especially translocations, in 7/14 (50%) patients with del 11q observed in FISH. DSP30 revealed cytogenetic anomalies which were not searched by FISH in 33/56 (59%) patients. The most frequently observed numerical aberrations were: monosomy 9 (n = 2), monosomy 10 (n = 2), monosomy 13 (n = 2), monosomy 14 (n = 2), monosomy 18 (n = 2) and loss of chromosome Y (n = 2).
It seems to me that complete karyotyping of CLL cells is now possible for all cytogenetics labs, and that it should be added to FISH for patients undergoing clinical trials.
The standard way of looking at chromosomes is to make cells divide, but in CLL this is very difficult. You need a mitogen and the standard mitogen is phorbol ester. Unfortunately although our lab gets over 80% of CLL cells to divide, nobocy else in the world can match our results. This has led other labs to experiment with cytokines to stimulate the CLL cells to divide.
In this month's Leukemia Research, a paper from Poland describes the use of a new mitogen, DSP30. DSP30 is a CpG-oligonucleotide (CpG-ODN). CpG-ODNs act as danger signals and stimulate the immune system. It induces proliferation
of both normal and leukemic B lymphocytes, stimulates production of cytokines, including IL-2 and TNF- , and regulates expression of surface antigens CD25 and CD86 in B lymphocytes. It also stimulates some other immune system cells, such as T lymphocytes, NK cells, dendritic cells and monocytes, to proliferate, secrete cytokines and/or differentiate.
Using DSP30, a sufficient number of metaphases suitable for analysis was obtained in 56/62 (90%) patients, and clonal chromosomal aberrations were detected in 42/56 (75%) patients. Normal karyotype was established in 14/56 (25%). In 9/14 (64%) cases with normal karyotype, aberrations were detected by FISH which revealed anomalies in 52/62 (84%) patients. Using DSP30 and/or FISH, aberrations were detected in 56/62
(90%) patients. DSP30 disclosed del 13q in only 10/56 (18%) cases, while FISH showed this anomaly in 41/62 (66%) subjects. Del 13q was cryptic and not detected by DSP30 in 28 patients. In those cases the presence of submicroscopic del 13q was confirmed by FISH on metaphases. In 4/41 (9.7%) patients del 13q were biallelic or concomitant monoallelic and biallelic. In 26/41 (63%) patients del 13q detected by FISH was a sole anomaly. Del 11q was detected by both FISH and DSP30 in 14 patients, whereas in two patients it was detected only by FISH due to an unsuccessful karyotyping. DSP30 enabled the detection of additional aberrations, especially translocations, in 7/14 (50%) patients with del 11q observed in FISH. DSP30 revealed cytogenetic anomalies which were not searched by FISH in 33/56 (59%) patients. The most frequently observed numerical aberrations were: monosomy 9 (n = 2), monosomy 10 (n = 2), monosomy 13 (n = 2), monosomy 14 (n = 2), monosomy 18 (n = 2) and loss of chromosome Y (n = 2).
It seems to me that complete karyotyping of CLL cells is now possible for all cytogenetics labs, and that it should be added to FISH for patients undergoing clinical trials.
Sunday, July 17, 2011
John 5:37-38
And the Father who sent me has Himself testified concerning me. You have never heard His voice nor seen his form, nor does His word dwell in you for you do not believe the one He sent.
Although John's gospel does not record the voice from heaven at Jesus' baptism, it would have been a well known occasion that didn't need setting down, when John was writing. Yet Jesus stresses that his listeners had not heard his voice. Moses had heard the voice from the burning bush; Elijah had heard the still, small voice; Jacob had seen his form; so had Abraham; and his word had dwelt in Joshua and the psalmists. Jesus was the word of God and the Jews of his time had no time for him. I am Jewish enough to have been vulnerable to Hitler and I weep for my ancestors.
We learn in the letter to the Hebrews that Jesus is 'the exact representation of His being'. The Jews who were his inquisitors were guilty of the one unforgivable sin - unbelief.
Although John's gospel does not record the voice from heaven at Jesus' baptism, it would have been a well known occasion that didn't need setting down, when John was writing. Yet Jesus stresses that his listeners had not heard his voice. Moses had heard the voice from the burning bush; Elijah had heard the still, small voice; Jacob had seen his form; so had Abraham; and his word had dwelt in Joshua and the psalmists. Jesus was the word of God and the Jews of his time had no time for him. I am Jewish enough to have been vulnerable to Hitler and I weep for my ancestors.
We learn in the letter to the Hebrews that Jesus is 'the exact representation of His being'. The Jews who were his inquisitors were guilty of the one unforgivable sin - unbelief.
Saturday, July 16, 2011
CS Lewis an evangelical?
Was CS Lewis an evangelical?
I think we can say categorically that he was not. Of course, he was a man of his generation. He denies being a fundamentalist, although he was accused of it because he refused to categorize any narrative as unhistorical because it contained miracles. Some people found miracles so hard to believe that they could not imagine any reason for CS Lewis to believe them other than a belief that every sentence of the Old Testament has historical or scientific truth. But this went much further than he would go. He was a creationist, but not a six-day creationist, but he also believed in purgatory (largely because he could not conceive that a sinner like him should be let into heaven without some serious scrubbing).
His profession was literary criticism and he applied his techniques to the Bible. His prejudice was that it was true, but he recognised different types of truth. Take the book of Job, for example. Along with Jean Calvin, he doubted whether it was historically true, rather than a work of fiction, like the Prodigal Son or the Good Samaritan, told to make an important point. He would not say it was not historical, but Job has no connection with any history or even legend, with no genealogy, living in an undescribed country, and the story is written as a storyteller would tell it.
He would accept that some early stories of Genesis come from an oral tradition and may have altered over time. We know that the Jews took inordinate means that the written text was preserved intact, though was there a time when alterations in the oral tradition could have been interpolated? But he also believed that the Holy Spirit took tremendous trouble to preserve his message in Scripture, through the agency of the church. This means that he has a greater respect for the Catholic church than we evangelicals might have. He says elsewhere that the differences between different branches of the church might turn out to be mere semantics when we get to heaven.
I would not be too quick to criticize other Christians and the grounds of semantics.
I quote from Reflections on the Psalms. "We may observe that the teaching of Our Lord Himself in which there is no imperfection, is not given us in that cut-and-dried, fool-proof, systematic fashion we might have expected or desired. He wrote no book. We only have reported sayings, most of them uttered in answer to questions, shaped in some degree by their context. And when we have collected them all, we cannot reduce them to a system. He preaches but he does not lecture. He uses paradox, proverb, exaggeration, parable, irony; even the 'wisecrack'. He utters maxims which like popular proverbs, if rigorously taken , may seem to contradict one another. His teaching therefore cannot be grasped by the intellect alone, cannot be 'got up' as if it were an academic subject. If we try to do that with it, we shall find Him the most elusive of teachers. He hardly ever gives a straight answer to a straight question. He will not be pinned down. The attempt is like trying to bottle a sunbeam."
I take this to mean that Lewis thinks that the Scripture is much more dynamic than we evangelicals take it to be. It is more open to interpretation guided by the Holy Spirit and that there are still truths to emerge that are not in the commentaries.
I think he would say that the New Testament characters acted in just this way. For example with the two on the road to Emmaus Jesus taught what it said about Himself from the Pentateuch and the prophets. Before Jesus much of what he revealed would have been interpreted differently by the Jewish teachers. Undoubtedly there are Messianic passages , but would the suffering servant have been seen as Messianic? Probably not.
But we have Phillip opening up Isaiah 53 directly with Jesus in mind to the Ethiopian eunuch. Before that passage in Acts, the suffering would have been thought of as referring to the nation of Israel itself. Jesus identified himself with the sufferer in Psalm 22 (My God, My God, why hast thou deserted me ... ) He asks how Christ could be both David's son and David's lord identifying himself as 'my Lord' in Psalm 110. He applied Psalm 91:11-12 to himself (He shall give his angels charge over thee ... that thou hurt not thy foot against a stone.) Psalm 118:22 (neither shalt thou suffer thy Holy One to see corruption) is appropriated as a prophesy of the resurrection in Acts 2.
Most have difficulty with uncertainty. With Scripture, I am afraid that we have to live with uncertainty. Even the most convincing commentater will admit to pasages with alternative explanation. No systematic theology is entirely convincing on every point. Lewis is vaguer than most and leaves many points undetermined, yet what he is sure about he puts beautifuly clearly. There has been too much Lewis worshipping for my taste and he would have hated it. He regarded himself as an amateur theologian and a professional student of literture, especially teh ancient literature of many traditions. He brought that studen's eye and insight into his studies of Scripture and he was always open to another interpretaion. I admire his intellect and his writing style, but I know he could sometimes be profoundly wrong.
I think we can say categorically that he was not. Of course, he was a man of his generation. He denies being a fundamentalist, although he was accused of it because he refused to categorize any narrative as unhistorical because it contained miracles. Some people found miracles so hard to believe that they could not imagine any reason for CS Lewis to believe them other than a belief that every sentence of the Old Testament has historical or scientific truth. But this went much further than he would go. He was a creationist, but not a six-day creationist, but he also believed in purgatory (largely because he could not conceive that a sinner like him should be let into heaven without some serious scrubbing).
His profession was literary criticism and he applied his techniques to the Bible. His prejudice was that it was true, but he recognised different types of truth. Take the book of Job, for example. Along with Jean Calvin, he doubted whether it was historically true, rather than a work of fiction, like the Prodigal Son or the Good Samaritan, told to make an important point. He would not say it was not historical, but Job has no connection with any history or even legend, with no genealogy, living in an undescribed country, and the story is written as a storyteller would tell it.
He would accept that some early stories of Genesis come from an oral tradition and may have altered over time. We know that the Jews took inordinate means that the written text was preserved intact, though was there a time when alterations in the oral tradition could have been interpolated? But he also believed that the Holy Spirit took tremendous trouble to preserve his message in Scripture, through the agency of the church. This means that he has a greater respect for the Catholic church than we evangelicals might have. He says elsewhere that the differences between different branches of the church might turn out to be mere semantics when we get to heaven.
I would not be too quick to criticize other Christians and the grounds of semantics.
I quote from Reflections on the Psalms. "We may observe that the teaching of Our Lord Himself in which there is no imperfection, is not given us in that cut-and-dried, fool-proof, systematic fashion we might have expected or desired. He wrote no book. We only have reported sayings, most of them uttered in answer to questions, shaped in some degree by their context. And when we have collected them all, we cannot reduce them to a system. He preaches but he does not lecture. He uses paradox, proverb, exaggeration, parable, irony; even the 'wisecrack'. He utters maxims which like popular proverbs, if rigorously taken , may seem to contradict one another. His teaching therefore cannot be grasped by the intellect alone, cannot be 'got up' as if it were an academic subject. If we try to do that with it, we shall find Him the most elusive of teachers. He hardly ever gives a straight answer to a straight question. He will not be pinned down. The attempt is like trying to bottle a sunbeam."
I take this to mean that Lewis thinks that the Scripture is much more dynamic than we evangelicals take it to be. It is more open to interpretation guided by the Holy Spirit and that there are still truths to emerge that are not in the commentaries.
I think he would say that the New Testament characters acted in just this way. For example with the two on the road to Emmaus Jesus taught what it said about Himself from the Pentateuch and the prophets. Before Jesus much of what he revealed would have been interpreted differently by the Jewish teachers. Undoubtedly there are Messianic passages , but would the suffering servant have been seen as Messianic? Probably not.
But we have Phillip opening up Isaiah 53 directly with Jesus in mind to the Ethiopian eunuch. Before that passage in Acts, the suffering would have been thought of as referring to the nation of Israel itself. Jesus identified himself with the sufferer in Psalm 22 (My God, My God, why hast thou deserted me ... ) He asks how Christ could be both David's son and David's lord identifying himself as 'my Lord' in Psalm 110. He applied Psalm 91:11-12 to himself (He shall give his angels charge over thee ... that thou hurt not thy foot against a stone.) Psalm 118:22 (neither shalt thou suffer thy Holy One to see corruption) is appropriated as a prophesy of the resurrection in Acts 2.
Most have difficulty with uncertainty. With Scripture, I am afraid that we have to live with uncertainty. Even the most convincing commentater will admit to pasages with alternative explanation. No systematic theology is entirely convincing on every point. Lewis is vaguer than most and leaves many points undetermined, yet what he is sure about he puts beautifuly clearly. There has been too much Lewis worshipping for my taste and he would have hated it. He regarded himself as an amateur theologian and a professional student of literture, especially teh ancient literature of many traditions. He brought that studen's eye and insight into his studies of Scripture and he was always open to another interpretaion. I admire his intellect and his writing style, but I know he could sometimes be profoundly wrong.
John 5:36. The testimony of miracles.
I have testimony weightier than that of John. For the very work that the Father has given me to finish, and which I am doing, testifies that the Father has sent me.
Water into wine, healing the official's son, healing the paralytic; you don't see things like that every day. If you imagine that these things can be done without the intervention of a higher authority, you are more gullible than the ordinary Joe. They couldn't move against Jesus without a better explanation. There will be more impressive works than these to come.
Water into wine, healing the official's son, healing the paralytic; you don't see things like that every day. If you imagine that these things can be done without the intervention of a higher authority, you are more gullible than the ordinary Joe. They couldn't move against Jesus without a better explanation. There will be more impressive works than these to come.
Cell phones
Steven King wrote a novel about cell phones called Cell. Everyone who was using their phone at a particular time was turned into a zombie. I believe it's true. I've seen them on the train from London. "Hello. I'm on the train. I'm shouting in case anyone else in the carriage can't hear me!"
Now a major storm has arisen over cell phone hacking. I have a confession. I own a cell phone. Early in its life I managed to press a button which stopped it ringing and it hasn't rung since. I have no idea how to restore its ring nor any interest in doing so. It has become an out-only phone; very useful for carrying in the car in case of a breakdown.
Apparently, it is possible to listen to the voice-mail of other people's cell phones. All you do is ring the number when no-one is available and you get switched to voice mail. Then you enter the manufacturer's default number and the phone gives you access to previous voice mail. It is easily guarded against by simply changing the default code to one you have made up. Journalists have known about this for many years and so have most members of the public like me, who know very little else about cell phones. Some years ago the England football manager was discovered to be having an affair with a TV weather girl. It was by this sort of phone hacking that the newspaper (I think the Daily Mail) found out about it. I'm surprised it still goes on when the remedy is so obvious, but apparently it does.
This simple activity has just brought down a major newspaper and severely affected an important industry. The News of the World was the largest selling British Newspaper. Its forte was exposing the sexual peccadillo's of Church of England clerics. I learned to read at the age of 2 by looking at the football results in the News of the World. Sad to see it go. Although this newspaper was the greatest offender in the phone hacking stakes it was by no means the only one. Indeed the Trinity Mirror Group (which owns the Daily Mirror) and the Associated Newspapers Group (which owns the Daily Mail) have been more involved in phone hacking than the News International Group (which owns the News of the World and the Sun). You might ask why this has all redounded on News International.
The answer is complex. First, the people who were affected by phone hacking are the sort of people who nobody cares about; buffoons like John Prescott and bimbos like Sienna Miller (I can hear you asking 'who she?').
Second, because nobody really cared, the police dragged their heels over the affair; worse than that they were in a cosy relationship with journalists, accepting illegal payments for information and not asking too many questions.
Third a particular episode of phone hacking surfaced at a murder trial. It appears that the phone of missing schoolgirl, Millie Dowler, was hacked and voice mail removed to unblock a full phone. This gave the impression that Millie was still alive - much to the distress of her parents. This discovery led to the discovery that other victims had been in similar situation, touching on the two little girls murdered at Souham, soldiers killed in Afghanistan and even victims of 7/7 and 9/11. The public may not care about buffoons and bimbos, but they certainly do about murder victims, shot soldiers and victims of atrocities.
Fourth, Rupert Murdoch is a hate-figure in left-wing circles. At the last general election he changed sides. His newspapers had been supporting his friend Tony Blair previously, but he switched to supporting his new friend David Cameron. Betrayal is a common feature of left-wing politics (read about Stalinist USSR) and this campaign has been driven by the Guardian and the BBC. They are even angry that Tony Blair was seduced by Murdoch in the first place - but would he have won three elections without Murdoch?
I expect that when the Judicial Enquiry reports we shall see that all red-top newspapers were equally at fault and there will be some rearrangement of the deck chairs. Probably the police will carry the can. The Press Complaints Commission will have new staff and a slightly different remit. The Parliamentary Lobby system will change and politicians will find more underhand ways to get into bed with journalists.
Now a major storm has arisen over cell phone hacking. I have a confession. I own a cell phone. Early in its life I managed to press a button which stopped it ringing and it hasn't rung since. I have no idea how to restore its ring nor any interest in doing so. It has become an out-only phone; very useful for carrying in the car in case of a breakdown.
Apparently, it is possible to listen to the voice-mail of other people's cell phones. All you do is ring the number when no-one is available and you get switched to voice mail. Then you enter the manufacturer's default number and the phone gives you access to previous voice mail. It is easily guarded against by simply changing the default code to one you have made up. Journalists have known about this for many years and so have most members of the public like me, who know very little else about cell phones. Some years ago the England football manager was discovered to be having an affair with a TV weather girl. It was by this sort of phone hacking that the newspaper (I think the Daily Mail) found out about it. I'm surprised it still goes on when the remedy is so obvious, but apparently it does.
This simple activity has just brought down a major newspaper and severely affected an important industry. The News of the World was the largest selling British Newspaper. Its forte was exposing the sexual peccadillo's of Church of England clerics. I learned to read at the age of 2 by looking at the football results in the News of the World. Sad to see it go. Although this newspaper was the greatest offender in the phone hacking stakes it was by no means the only one. Indeed the Trinity Mirror Group (which owns the Daily Mirror) and the Associated Newspapers Group (which owns the Daily Mail) have been more involved in phone hacking than the News International Group (which owns the News of the World and the Sun). You might ask why this has all redounded on News International.
The answer is complex. First, the people who were affected by phone hacking are the sort of people who nobody cares about; buffoons like John Prescott and bimbos like Sienna Miller (I can hear you asking 'who she?').
Second, because nobody really cared, the police dragged their heels over the affair; worse than that they were in a cosy relationship with journalists, accepting illegal payments for information and not asking too many questions.
Third a particular episode of phone hacking surfaced at a murder trial. It appears that the phone of missing schoolgirl, Millie Dowler, was hacked and voice mail removed to unblock a full phone. This gave the impression that Millie was still alive - much to the distress of her parents. This discovery led to the discovery that other victims had been in similar situation, touching on the two little girls murdered at Souham, soldiers killed in Afghanistan and even victims of 7/7 and 9/11. The public may not care about buffoons and bimbos, but they certainly do about murder victims, shot soldiers and victims of atrocities.
Fourth, Rupert Murdoch is a hate-figure in left-wing circles. At the last general election he changed sides. His newspapers had been supporting his friend Tony Blair previously, but he switched to supporting his new friend David Cameron. Betrayal is a common feature of left-wing politics (read about Stalinist USSR) and this campaign has been driven by the Guardian and the BBC. They are even angry that Tony Blair was seduced by Murdoch in the first place - but would he have won three elections without Murdoch?
I expect that when the Judicial Enquiry reports we shall see that all red-top newspapers were equally at fault and there will be some rearrangement of the deck chairs. Probably the police will carry the can. The Press Complaints Commission will have new staff and a slightly different remit. The Parliamentary Lobby system will change and politicians will find more underhand ways to get into bed with journalists.
Friday, July 15, 2011
John 5:33-34. Whose testimony?
You have sent to John and he has testified to the truth. Not that I accept human testimony, but I mention it that you may be saved.
Jesus is playing with them. He is teasing them. He is concerned that they may be saved and by reminding them of John's testimony he wonders if they may have listened to him since only believing in Jesus will save them. But he has better testimony that John's.
Jesus is playing with them. He is teasing them. He is concerned that they may be saved and by reminding them of John's testimony he wonders if they may have listened to him since only believing in Jesus will save them. But he has better testimony that John's.
Who should have prognostic markers done and when?
Why should I get my prognostic markers done? Many people have decided not to get their markers tested for very good reasons. They just want to get on with their lives and the future will come soon enough. However, just like we watch the weather forecasts many of us do want to know something about the future so we can plan for it.
I think it goes without saying that anyone who needs treatment should have his TP53 status established. Response to conventional drugs in CLL is severely impaired in TP53 deficient patients and why suffer the toxicity of fludarabine if it isn't going to work? Generally this means a FISH test for del 17p. In my opinion knowing that you are del 13q, or trisomy 12 isn't going to give you any extra information and unless these come as a cheap package, I wouldn't bother with them at this stage.
The other markers that matter of IGHV mutations, CD38, ZAP-70, beta2M and del 11q. These will not affect the response to treatment, at least not when judged by rate of CR and PR, though they might affect MRD negativity. What they do affect is length of remission and overall survival. The IGHV mutation status affects these things from the time of diagnosis, and ZAP-70 expression done by the Crespo method or the Orchard method is a close correlate of that. ZAP-70 done by the Rassenti method is an independent prognostic factor and when done by commercial labs is so unreliable as not to be recommended.
CD38 is changeable, so at diagnosis it may be low but as the disease progresses it tends to increase. The same is true to some extent of Beta2M.
A lot of thought is spent on whether to choose FR or FCR, or between FCR and PCR and even if Bendamustine might not be a better bet, but what influences outcome most is not which treatment is chosen but whether or not the IGHV genes are mutated or unmutated. This does not change during the course of disease and only needs to be done once, at diagnosis.
In about a third of cases the markers are uniformly bad and in about a third they are uniformly good. It is the middle third where confusion lies. In my experience these patients have an intermediate prognosis. This is often because the CD38 is low and will be raised later in the course of the disease, but sometimes it is because the CLL cell has found another way of signaling through to second messengers in the cell that by-pass the B-cell receptor's usual pathway.
Del 11q was always thought of as a poor prognostic marker, but the addition of rituximab to therapeutic mixtures has meant that remissions have been just as long as for those without del 11q. However, a caveat: on the grapevine I hear that this may not remain true as the trials become more mature. We wait and see.
This is what I recommend for patients who have CLL.
Group 1. Those patients with MBL and those who truly do not want to know, do not do any but the diagnostic markers (CD5, CD19, CD20, CD23, CD79b, surface Ig, FMC7).
Group 2. Those who do want some idea of the future, IGHV mutations, Beta2M and CD38. In certain circumstances (if you are lucky enough to be under a Consortioum Center) ZAP-70. Don't be content with just the mutated/unmutated result; ask which gene is being used and whether it belongs to one of the stereotypes.
Group 3. If you have unmutated IGHV genes and low CD38 and Beta2M, get these measured every year. There is no need to repeat the IGHV mutations; these will not change.
Group 4. If you are about to start treatment either for the first or subsequent time you must have FISH for Del 17p and preferably at the moment for Del 11q. At the moment there is no need to test for trisomy 12 or del 13q, but if these are available in a cheap package you may as well since I do believe that as more knowledge accumulates they will be useful. With del 13q it is likely to be the size of the deletion that is important. It is always better to get the markers done at research labs rather than at commercial labs, because they often obtain more information than you pay for and as time passes that information becomes useful. I am still waiting to see what becomes of the information that those with trisomy 12 often have trisomy 16 and sometimes 18 or 19 as well. They may all belong to a single stereotype.
There is evidence that mutated and unmutated respond equally well to PCI32765 and CAL101. Yes, but they respond equally well to fludarabine. It is length of remission and overall survival where things differ.
I think it goes without saying that anyone who needs treatment should have his TP53 status established. Response to conventional drugs in CLL is severely impaired in TP53 deficient patients and why suffer the toxicity of fludarabine if it isn't going to work? Generally this means a FISH test for del 17p. In my opinion knowing that you are del 13q, or trisomy 12 isn't going to give you any extra information and unless these come as a cheap package, I wouldn't bother with them at this stage.
The other markers that matter of IGHV mutations, CD38, ZAP-70, beta2M and del 11q. These will not affect the response to treatment, at least not when judged by rate of CR and PR, though they might affect MRD negativity. What they do affect is length of remission and overall survival. The IGHV mutation status affects these things from the time of diagnosis, and ZAP-70 expression done by the Crespo method or the Orchard method is a close correlate of that. ZAP-70 done by the Rassenti method is an independent prognostic factor and when done by commercial labs is so unreliable as not to be recommended.
CD38 is changeable, so at diagnosis it may be low but as the disease progresses it tends to increase. The same is true to some extent of Beta2M.
A lot of thought is spent on whether to choose FR or FCR, or between FCR and PCR and even if Bendamustine might not be a better bet, but what influences outcome most is not which treatment is chosen but whether or not the IGHV genes are mutated or unmutated. This does not change during the course of disease and only needs to be done once, at diagnosis.
In about a third of cases the markers are uniformly bad and in about a third they are uniformly good. It is the middle third where confusion lies. In my experience these patients have an intermediate prognosis. This is often because the CD38 is low and will be raised later in the course of the disease, but sometimes it is because the CLL cell has found another way of signaling through to second messengers in the cell that by-pass the B-cell receptor's usual pathway.
Del 11q was always thought of as a poor prognostic marker, but the addition of rituximab to therapeutic mixtures has meant that remissions have been just as long as for those without del 11q. However, a caveat: on the grapevine I hear that this may not remain true as the trials become more mature. We wait and see.
This is what I recommend for patients who have CLL.
Group 1. Those patients with MBL and those who truly do not want to know, do not do any but the diagnostic markers (CD5, CD19, CD20, CD23, CD79b, surface Ig, FMC7).
Group 2. Those who do want some idea of the future, IGHV mutations, Beta2M and CD38. In certain circumstances (if you are lucky enough to be under a Consortioum Center) ZAP-70. Don't be content with just the mutated/unmutated result; ask which gene is being used and whether it belongs to one of the stereotypes.
Group 3. If you have unmutated IGHV genes and low CD38 and Beta2M, get these measured every year. There is no need to repeat the IGHV mutations; these will not change.
Group 4. If you are about to start treatment either for the first or subsequent time you must have FISH for Del 17p and preferably at the moment for Del 11q. At the moment there is no need to test for trisomy 12 or del 13q, but if these are available in a cheap package you may as well since I do believe that as more knowledge accumulates they will be useful. With del 13q it is likely to be the size of the deletion that is important. It is always better to get the markers done at research labs rather than at commercial labs, because they often obtain more information than you pay for and as time passes that information becomes useful. I am still waiting to see what becomes of the information that those with trisomy 12 often have trisomy 16 and sometimes 18 or 19 as well. They may all belong to a single stereotype.
There is evidence that mutated and unmutated respond equally well to PCI32765 and CAL101. Yes, but they respond equally well to fludarabine. It is length of remission and overall survival where things differ.
Thursday, July 14, 2011
John 5:32. Who is the other witness?
There is another who testifies in my favor, and I know that his testimony about me is valid
We know that the 'another' is the Father, but Jesus is not revealing this just yet. He will go on to list other witnesses, but from what has preceded this, we know he must mean the Father.
We know that the 'another' is the Father, but Jesus is not revealing this just yet. He will go on to list other witnesses, but from what has preceded this, we know he must mean the Father.
Praise
Here's a wake up call to any medical teachers out there; do you praise your fellows?
Eddie Blackburn, who was Professor of Haematology at Sheffield, used to make a habit of writing a letter praising the authors of papers that he read in the British Journal of Haematology.
William Mayo, the founder of the Mayo Clinic used praise to encourage young doctors.
One of them said, "You'd read a paper at a staff meeting and afterwards he'd see you in the lift or the hall, and would shake your hand and put his hand on your shoulder with a quiet, 'Good work,' and a straight warm look that made you think he meant it. Or perhaps a day or two later you'd get a note from him, just a short one saying something like, 'Dear -------, I learned more about ------- from that paper of yours the other night than I ever knew before. It was a good job.' Believe me, a fellow prized those notes."
Eddie Blackburn, who was Professor of Haematology at Sheffield, used to make a habit of writing a letter praising the authors of papers that he read in the British Journal of Haematology.
William Mayo, the founder of the Mayo Clinic used praise to encourage young doctors.
One of them said, "You'd read a paper at a staff meeting and afterwards he'd see you in the lift or the hall, and would shake your hand and put his hand on your shoulder with a quiet, 'Good work,' and a straight warm look that made you think he meant it. Or perhaps a day or two later you'd get a note from him, just a short one saying something like, 'Dear -------, I learned more about ------- from that paper of yours the other night than I ever knew before. It was a good job.' Believe me, a fellow prized those notes."
Wednesday, July 13, 2011
John 5:31. Many witnesses.
If I testify about myself, my testimony is not valid.
No-one likes someone who blows their own horn. Jesus had a 'sign' ministry. The miracles spoke for themselves. Had he just worked on the Sabbath or made what were considered blasphemous statements about himself the the Jews would have felt very safe in stoning him. But the signs were there or all to see. They would later accuse him of doing these miracles by devilish means, but while the people were behind him their hands were tied.
Jesus would go on to develop the theme that there were yet other witnesses to who he was.
No-one likes someone who blows their own horn. Jesus had a 'sign' ministry. The miracles spoke for themselves. Had he just worked on the Sabbath or made what were considered blasphemous statements about himself the the Jews would have felt very safe in stoning him. But the signs were there or all to see. They would later accuse him of doing these miracles by devilish means, but while the people were behind him their hands were tied.
Jesus would go on to develop the theme that there were yet other witnesses to who he was.
Tuesday, July 12, 2011
T-cells are important in CLL
Nick Chiorazzi's group have published a paper in Blood that shows a method that enables mature CLL cells to grow in a mouse model. They use a nonobese diabetes/severe combined immunodeficincy/gammacnull mouse into which they introduce precursors of human hematopoietic and mesenchymal lineages. It had been previously found that in order for CLL cells to fail to be rejected by a mouse, it has to be very immuno-incompetent indeed. A NOD/SCID mouse lacks the IL-2 family common cytokine receptor gamma chain gene rendering the animal completely deficient in lymphocytes including NK cells. In addition, CLL cells require the support of T cells, monocytes and monocyte-derived nurse-like cells and stromal cells.
They established that autologous CD3+, CD4+ T cells were necessary for CLL engraftment and proliferation, whereas murine stroma and monocyte-derived lineages are quite sufficient to support growth. Another human cell type that facilitated growth in this model was allogeneic antigen presnting cells (either CD14+ or CD19+). This suggests that activation of T cells in necessary for the facilitation of CLL growth to occur.
It may be that the effectiveness of T-cell toxic drugs like fludarabine and Campath derives from their ability to kill T cells. Possibly the importance of T/B interactions is reflected in some of the epiphenomena of CLL such as second malignancies, immunodeficiency and autoimmunity.
They established that autologous CD3+, CD4+ T cells were necessary for CLL engraftment and proliferation, whereas murine stroma and monocyte-derived lineages are quite sufficient to support growth. Another human cell type that facilitated growth in this model was allogeneic antigen presnting cells (either CD14+ or CD19+). This suggests that activation of T cells in necessary for the facilitation of CLL growth to occur.
It may be that the effectiveness of T-cell toxic drugs like fludarabine and Campath derives from their ability to kill T cells. Possibly the importance of T/B interactions is reflected in some of the epiphenomena of CLL such as second malignancies, immunodeficiency and autoimmunity.
JE Trapnell RIP
John Eliot Trapnell, consultant surgeon, has died aged 81. John was my mentor in surgery. I first met him as a medical student when he was a registrar in Bristol. He was born a Bristolean and was educated at Clifton College, the famous Public School where the highest score in cricket was made in Victorian times (Arthur Collins scored 628 not out over four afternoons in June 1899 when he was 13 years old).
John graduated BA from Trinity College Cambridge in 1951 and MB.BChir in 1954, having done his clinical training at the Middlesex Hospital. He achieved a Cambridge MD in 1966. House jobs at the Middlesex and Central Middlesex were followed by junior doctor training at Leicester and then service with the Church Missionary Society in Maseno in Kenya
Between 1960 and 1968 he was a Registrar and Senior Registrar on the Bristol rotation, which for him included a year in Philadelphia on a Fulbright Scholarship.
When I met John, he had a formidable reputation as a surgeon of the old school. He knew his own mind and was quite sure that he as a surgeon knew better what needed to be done than any mere physician. I remember as a house surgeon being asked to remove dead muscle from the leg of a man with end-stage cirrhosis. John was of the opinion that the leg needed to be amputated. He watched over me while I nibbled away at the ischemic leg. When I had finished he said, "Now they will believe me when I say it needs to be amputated."
John became consultant surgeon in Bournemouth in 1968 and had been here for 4 years before I came down as a Senior Registrar in Hematology. He always watched over me and was kind to me as my career progressed.
Shortly after I was converted he came and preached at my house at a meeting we held for those aged 20-40. I remember he preached on Exodus 15:22-27: the waters of Marah and Elim. For a long while he was an Anglican Lay Reader, but under the ministry of Harry Kilbride he was baptized as an adult believer, which upset some people. He later preached regularly at Anglican, Methodist, Baptist and Evangelical churches throughout Hampshire and Dorset and beyond.
As Senior Surgeon in Bournemouth he was hugely influential, affecting many changes while he was Chairman of the Medical Staff. He was greatly beloved of his patients though his colleagues sometimes required more patience with him. He could be forthright. His patients remember the kind way he always phoned up the spouse of the person he had just operated on to tell him or her that all was well.
He became a world authority on pancreatitis and cancer of the pancreas, publishing over 70 scientific and medical papers and 10 text-book chapters. He received many honors including the EK Frey Prize Medal of the German and Austrian Intensive Care Society. He held a Hunterian Professorship of the Royal College of Surgeons in 1969. He traveled widely as a visiting Professor in America, Europe and Asia and lecturer and examiner worldwide. He worked tirelessly to help foreign medical graduates in Africa and from behind the iron curtain obtain first class higher surgical training.
He retired at the age of 60 and had 21 years of retirement at his beautiful house on the edge of the New Forest. He died peacefully in his sleep in Cambridge following a reunion at Trinity College. He is survived by his wife Sandy and his four daughters from an earlier marriage.
John 5:30. A plethora of grace.
By myself I can do nothing; I judge only as I hear, and my judgement is just, for I seek not to please myself but him who sent me.
Shall not the judge of all the earth do right? asked Abraham as the LORD prepared to judge Sodom. So it shall be on that day of final judgement. There will be no side or bias to the judge of all the earth. Remember that if any man be in Hell it will be the result of human responsibility; if any man be in Heaven it be because of divine sovereignty. My only resort is to cast myself on the mercy of the court; but there is plenteous mercy available and free. In the midst of condemnation we swim in a plethors of grace.
Shall not the judge of all the earth do right? asked Abraham as the LORD prepared to judge Sodom. So it shall be on that day of final judgement. There will be no side or bias to the judge of all the earth. Remember that if any man be in Hell it will be the result of human responsibility; if any man be in Heaven it be because of divine sovereignty. My only resort is to cast myself on the mercy of the court; but there is plenteous mercy available and free. In the midst of condemnation we swim in a plethors of grace.
Monday, July 11, 2011
John 5:28-29.The marks of the saved
Do not be amazed at this, for a time is coming when all who are in their graves will hear his voice and come out—those who have done what is good will rise to live, and those who have done what is evil will rise to be condemned.
All will face judgement. I guess these verses put an end to those who say that all will be saved or those who say when we die we rot.
Note that it is men's doings that are judged. Calvin himself notes that the Lord is not speaking of the cause of salvation, which is the finished work of Christ, but the marks of the saved. It is good doing that distinguishes the elect from the reprobate. Otherwise we must believe that belief is work.
All will face judgement. I guess these verses put an end to those who say that all will be saved or those who say when we die we rot.
Note that it is men's doings that are judged. Calvin himself notes that the Lord is not speaking of the cause of salvation, which is the finished work of Christ, but the marks of the saved. It is good doing that distinguishes the elect from the reprobate. Otherwise we must believe that belief is work.
Sunday, July 10, 2011
Chukka weekend
We have had a busy weekend. Our son, David and girlfriend Charlotte have been staying with us. They have been exhibiting with their company, Chukka, at the British Beach Polo Championships at Sandbanks. It was a pukka event watched by a lot of rich people. The alcohol was flowing which lubricated their wallets.
It was not our sort of event, but the sun was shining with a cooling onshore breeze and some beach volleyball to watch as well. No William and Kate though.
David has also helped me to water-blast my dirty patio and restored the water feature in the garden where the pump had burnt out.
We also took their dog down on the beach at Hengistbury Head. I have found the weekend very tiring. I no longer have the strngth and stamina that I once had. I have to pace myself.
It was not our sort of event, but the sun was shining with a cooling onshore breeze and some beach volleyball to watch as well. No William and Kate though.
David has also helped me to water-blast my dirty patio and restored the water feature in the garden where the pump had burnt out.
We also took their dog down on the beach at Hengistbury Head. I have found the weekend very tiring. I no longer have the strngth and stamina that I once had. I have to pace myself.
John 5:27. Judged by our peer.
And he has given him authority to judge because he is the Son of Man
A man should be judged by his peers. Jesus was tempted in every way as we are. He was subject to the same privations, deficiencies, cruelties, psychological strain, and more so. He does not judge from some lofty plain but in his common humanity.
A man should be judged by his peers. Jesus was tempted in every way as we are. He was subject to the same privations, deficiencies, cruelties, psychological strain, and more so. He does not judge from some lofty plain but in his common humanity.
John 5:26. The Son has life in himself.
For as the Father has life in himself, so he has granted the Son to have life in himself.
The moon, the planets and, as we have seen from space exploration, the earth itself, have only reflected light from the sun. So it is with life on earth; we human beings together with every creature whether plant or animal or microbe only have life because of being created by one with life in himself. The Father has it and so does the Son.
Some theologians talk about the 'eternal generation of the Son'. It all depends what they mean by this, but it should imply that this granting of life to the Son was not something that began at the the incarnation, since John has already told us that 'all things were created by him.'
I like JC Ryle on this: The privileges of a true Christian are greatly underrated by many... One of a true Christians's treasures is the 'presentness' of his salvation. It is not a far distant thing which he has to have at last, if he does his duty and is good. It is his own in title the moment he believes. He is already pardoned, forgiven and saved - though not in heaven.
Another of his treasures is the 'completeness' of his justification. His sins are entirely removed, taken away and blotted out by Christ's blood. He may look forward to judgement without fear. He shall stand without fault before the throne of God.
The third treasure is the entire change in his relation and position towards God. He is no longer as one dead before him - dead legally, like a man sentenced to die, and dead in heart. He is alive unto God. He is a new creature. Old things are passed away and all things are become new.
The moon, the planets and, as we have seen from space exploration, the earth itself, have only reflected light from the sun. So it is with life on earth; we human beings together with every creature whether plant or animal or microbe only have life because of being created by one with life in himself. The Father has it and so does the Son.
Some theologians talk about the 'eternal generation of the Son'. It all depends what they mean by this, but it should imply that this granting of life to the Son was not something that began at the the incarnation, since John has already told us that 'all things were created by him.'
I like JC Ryle on this: The privileges of a true Christian are greatly underrated by many... One of a true Christians's treasures is the 'presentness' of his salvation. It is not a far distant thing which he has to have at last, if he does his duty and is good. It is his own in title the moment he believes. He is already pardoned, forgiven and saved - though not in heaven.
Another of his treasures is the 'completeness' of his justification. His sins are entirely removed, taken away and blotted out by Christ's blood. He may look forward to judgement without fear. He shall stand without fault before the throne of God.
The third treasure is the entire change in his relation and position towards God. He is no longer as one dead before him - dead legally, like a man sentenced to die, and dead in heart. He is alive unto God. He is a new creature. Old things are passed away and all things are become new.
Saturday, July 09, 2011
Praising God
One of the criticisms that Richard Dawkins has of the Christian God is that he is always demanding praise. the Psalms are particularly demanding in this respect. "Praise the Lord", "O praise the Lord with me", "Praise him".
This gels poorly with the English character which believes in public modesty. We despise the millionaire or celebrity of sportsman who always demands assurance of his own importance.
Even worse is the silly pagan bargaining that says we weill praise him if he does something for us. "Keep me alive because I can't praise you when I'm dead"
It is easy to be grateful to God, to be reverent towards him and obedient to him, but a continual cacophony of praise? Isn't that gilding the lilly?
We read elsewhere that He is worthy to be praised. And that is true. Even inanimate objects are sometimes thought to be admirable. We admire a landscape or a picture. We praise a TV program or a play. In fact we make ourselves look insensitive or obtuse if we don't The man who does not praise a wonderful piece of music or a good book or a bright morning or the love of a good woman or even an exciting cricket match is lacking in some way.
So it is with God. What he has created, the way he has dealt with his creation and above all the atoning sacrifice of Jesus, demands praise. Not in any creepy sense or from any vain desire. Indeed in Psalm 50 the Lord says, "If I were hungry, would I tell you?" If such an absurd thing could be contemplated why should he turn to us for supply?
For praise is a human reaction to excellence and we do it by sharing our approval with others. To start to applaud is to invite others to join in. Somehow the praise completes the enjoyment. The chief end of men is to glorify God and enjoy him forever. Not for his sake, but for ours.
This gels poorly with the English character which believes in public modesty. We despise the millionaire or celebrity of sportsman who always demands assurance of his own importance.
Even worse is the silly pagan bargaining that says we weill praise him if he does something for us. "Keep me alive because I can't praise you when I'm dead"
It is easy to be grateful to God, to be reverent towards him and obedient to him, but a continual cacophony of praise? Isn't that gilding the lilly?
We read elsewhere that He is worthy to be praised. And that is true. Even inanimate objects are sometimes thought to be admirable. We admire a landscape or a picture. We praise a TV program or a play. In fact we make ourselves look insensitive or obtuse if we don't The man who does not praise a wonderful piece of music or a good book or a bright morning or the love of a good woman or even an exciting cricket match is lacking in some way.
So it is with God. What he has created, the way he has dealt with his creation and above all the atoning sacrifice of Jesus, demands praise. Not in any creepy sense or from any vain desire. Indeed in Psalm 50 the Lord says, "If I were hungry, would I tell you?" If such an absurd thing could be contemplated why should he turn to us for supply?
For praise is a human reaction to excellence and we do it by sharing our approval with others. To start to applaud is to invite others to join in. Somehow the praise completes the enjoyment. The chief end of men is to glorify God and enjoy him forever. Not for his sake, but for ours.
Friday, July 08, 2011
Is O-FC as good as FCR?
The MDACC lot have published the results of a phase 2 trial of FC with Ofatumumab in 61 previously untreated CLL patients. The question we all want to know is whether O-FC is likely to be an improvement on FCR.
The problem with a phase 2 study is that there is no comparison that is valid. All you can do is look at other phase 2 studies and make a rough judgement.
So what is the competition like? The CALGB 9712 trial reported at CR rate of 47% and an OR rate of 90% for FR. The MDACC FCR response rate was 72% CR and 95% OR. The Spanish FCM-R rates were 82% CR and 93% OR. But the German CLL8 study reported a more realistic 44% CR rate and 95% OR, All these studies were in relatively young and fit patients.
However, the O-FC study was a bit more stringent in some respects, though not all. The patients were still young with a median age of 56, but they included 13% with a del 17p and 16% with del 11q. 64% had a Beta-2M level greater than 3.5. 47% were unmutated and 20% had a raised CD38. Of particular note was the OR of 63% and CR rate of 13% in del 17p patients.
The overall incidence of toxicity and failure to complete treatment was similar to the MDACC experience with FCR.
The FC was given in standard doses but the O was given as either 500 or 1000 mg (not per sq m). The OR rate was 77% and 73% for the two doses respectively (ie not statistically different) but the CR rate was 50% for the higher dose and 32% for the lower (not statistically different, though because of small numbers). By univariate analysis the factors determining response were completion of sufficient courses of treatment and the Beta-2M level.
What can we say then, is O-FC as good as FCR? This small study is unable to say more than it might be. We shall have to await head to head comparisons.
The problem with a phase 2 study is that there is no comparison that is valid. All you can do is look at other phase 2 studies and make a rough judgement.
So what is the competition like? The CALGB 9712 trial reported at CR rate of 47% and an OR rate of 90% for FR. The MDACC FCR response rate was 72% CR and 95% OR. The Spanish FCM-R rates were 82% CR and 93% OR. But the German CLL8 study reported a more realistic 44% CR rate and 95% OR, All these studies were in relatively young and fit patients.
However, the O-FC study was a bit more stringent in some respects, though not all. The patients were still young with a median age of 56, but they included 13% with a del 17p and 16% with del 11q. 64% had a Beta-2M level greater than 3.5. 47% were unmutated and 20% had a raised CD38. Of particular note was the OR of 63% and CR rate of 13% in del 17p patients.
The overall incidence of toxicity and failure to complete treatment was similar to the MDACC experience with FCR.
The FC was given in standard doses but the O was given as either 500 or 1000 mg (not per sq m). The OR rate was 77% and 73% for the two doses respectively (ie not statistically different) but the CR rate was 50% for the higher dose and 32% for the lower (not statistically different, though because of small numbers). By univariate analysis the factors determining response were completion of sufficient courses of treatment and the Beta-2M level.
What can we say then, is O-FC as good as FCR? This small study is unable to say more than it might be. We shall have to await head to head comparisons.
John 5:25. Waking the dead.
I tell you the truth, a time is coming and has now come, when the dead will hear the voice of the Son of God and those who hear will live
The expression relates to the future, when at the end time the voice of Jesus will wake the physically dead in a call to judgement AND to the present when the voice of Jesus will wake the spiritually dead.
The expression relates to the future, when at the end time the voice of Jesus will wake the physically dead in a call to judgement AND to the present when the voice of Jesus will wake the spiritually dead.
monotheism
Most primitive religions either set Nature as God or have a sort of Pantheistic aspect to them. The idea that there is an uncreated beginning, a single God who created everything is very rare. Plato stands out from the rest of the Greeks in believing in a single source. His concept of an invisible and supreme spiritual Being, is so different from the prevalent polytheism of other Greek philosophers and so remote from the pantheon of Homer and its scandalous Olympians with their permanent strife and marital and extra-marital affairs with mortal women, that one is inclined to think that Plato, at the time of his travel to Egypt thirty years old, happened to sit at the feet of Ezra. This would be around 400 BC or just after. It is easy to draw the conclusion that Plato's monotheism had a Mosaic source.
But Plato was not the first monotheistic, non-Semite. One of the Pharaohs, Amenhetep IV who called himself Akhenaten overthrew the prevailing polytheism in Egypt and set up a monotheistic religion. He is conventionally dated from the 14th century BC. Could he have been influenced by Jewish tradition?
The majority of modern scholars date the Patriarch Joseph to the Second Intermediate Period of Egyptian history, ca. 1786-1570 BC, a time when the Hyksos ruled the delta of the Nile. This view is based primarily on two assumptions: first, that the so-called Late Date of the Exodus during the reign of Ramses II is correct, and that the rise to power of an Asiatic like Joseph can best be placed during a period of Egyptian history when his fellow Asiatics, the Hyksos, controlled the government.
If the Exodus occurred in the 13th century BC, and the time in Egypt lasted approximately 400 years (430, according to Exodus 12:40), Joseph would belong in the 17th century BC. But if the Exodus took place in the 15th century BC as some suggest, Joseph's career would be shifted back to the 19th century BC, during the days of the 12th Dynasty of the Middle Kingdom. Such an early date might mean that the rule of the Hyskos was a consequence of the devastation of Egypt following the destruction of Pharaoh's army in the Red Sea.
1 Kings 6:1 dates the Exodus 480 years before the fourth year of Solomon, ca. 966 BC.
I am not sufficiently skilled in Egyptian chronology to judge between these dates and I suspect that each scholar who looks at the data has his own hobby-horse to ride. Some years ago I read a long and detailed book by Donavon Courville on this subject by an author who thought all the experts were wrong about the dating. His thesis was that several of the Dynasties overlapped.
In any event it could well be that the monotheism of Akhenaten also had a Hebraic origin.
But Plato was not the first monotheistic, non-Semite. One of the Pharaohs, Amenhetep IV who called himself Akhenaten overthrew the prevailing polytheism in Egypt and set up a monotheistic religion. He is conventionally dated from the 14th century BC. Could he have been influenced by Jewish tradition?
The majority of modern scholars date the Patriarch Joseph to the Second Intermediate Period of Egyptian history, ca. 1786-1570 BC, a time when the Hyksos ruled the delta of the Nile. This view is based primarily on two assumptions: first, that the so-called Late Date of the Exodus during the reign of Ramses II is correct, and that the rise to power of an Asiatic like Joseph can best be placed during a period of Egyptian history when his fellow Asiatics, the Hyksos, controlled the government.
If the Exodus occurred in the 13th century BC, and the time in Egypt lasted approximately 400 years (430, according to Exodus 12:40), Joseph would belong in the 17th century BC. But if the Exodus took place in the 15th century BC as some suggest, Joseph's career would be shifted back to the 19th century BC, during the days of the 12th Dynasty of the Middle Kingdom. Such an early date might mean that the rule of the Hyskos was a consequence of the devastation of Egypt following the destruction of Pharaoh's army in the Red Sea.
1 Kings 6:1 dates the Exodus 480 years before the fourth year of Solomon, ca. 966 BC.
I am not sufficiently skilled in Egyptian chronology to judge between these dates and I suspect that each scholar who looks at the data has his own hobby-horse to ride. Some years ago I read a long and detailed book by Donavon Courville on this subject by an author who thought all the experts were wrong about the dating. His thesis was that several of the Dynasties overlapped.
In any event it could well be that the monotheism of Akhenaten also had a Hebraic origin.
Afghanistan
You would have thought that it was a relatively simple matter for our troops to guard against improvised explosive devices in Afghanistan. Michael Yon explains some of the tricks of the trade here.
Thursday, July 07, 2011
Women's rights in increasingly Islamic Turkey
Why is Turkey's AKP ruling party opposing efforts to protect women? Because the Qur'an directs men to beat disobedient women (4:34); how, then, is all this domestic violence any concern of a good, pious Muslim?
Prime Minister Erdoğan of Turkey announced last month that the "Ministry for Women and Family" will be replaced by a "Ministry of Family and Social Policies," ending explicit focus on women's rights. This is much more than just a name change and signals a reduced emphasis on women's rights, and efforts to promote the rights to non-discrimination and freedom from violence will suffer. Rather than taking the spotlight off women's rights, Turkey needs to take urgent steps to combat endemic violence against women. In the past 10 years since the government has becaome less secular and more Islamic violent deaths of women have risen from less tha 100 a year to nearly 2000.
The existing ministry's mandate was dedicated to working on issue relating to women's rights and the family. The new ministry, however, will deal with issues of concern relating to children, the aged, the disabled, and the families of soldiers who die during active service, as well as family and women's rights. The existing Directorate for the Status of Women will be a department within the ministry.
A Human Rights Watch report issued in May documents brutal and long-lasting violence against women and girls in Turkey by husbands, partners, and family members, and the survivors' struggle to get protection. A study by Turkey's Hacettepe University has shown that about 42 percent of Turkish women experience physical or sexual violence inflicted by a relative at some point in their lives.
Turkey has improved its laws, setting out requirements for shelters for abused women and protection orders. However, gaps in the law and implementation failures by police, prosecutors, judges, and other officials make the protection system unpredictable at best, and at times downright dangerous.
In addition to the high rates of domestic violence in Turkey, other statistics speak to broader gender inequality in the country. In 2010, Turkey ranked 83 on the United Nations Development Programme's global Gender Inequality Index - down six places compared with 2008. Women hold just 9 percent of seats in the national parliament, and only 27 of the country's nearly 3,000 mayors are women.
Women are 27 percent of the paid work force. Only about 19 percent of women are engaged in income-generating work in Turkey, and in the eastern part of the country, the figure is about 10 percent. Illiteracy figures released by the government show great disparities between men and women: 3.8 million of the 4.7 million people who are illiterate are women.
Nearly 50 percent of the women in Turkey’s Eastern city of Şanlıurfa give birth at home. Women do not know that to put henna in the belly button of a baby might be deadly as the baby might get infected. To the contrary they think it is good for the health of the new born. It is a matter of shame to go and see a doctor. Being beaten up is routine. Doing something other than working in the fields is enough to be labeled “bad women.”
Zeynep Şimşek, from Urfa’s Harran University, decided to take the challenge, and women from Şanlıurfa have come to see the head of the University’s Public Health Department as a super hero. As she knew how things worked in one of the most conservative cities in Turkey, Şimşek first tried to convince the men before the women. She first started by training the local headmen. She provided essential information about women's and children's health. She taught them the answers of what to do during pregnancy, how to help women who are victims of domestic violence, where they can go and what their legal rights are. When the local headmen told her, “As men how can we explain all these things to the women? Why don’t you come and tell them yourself?” she caught the opportunity to reach women individually.
Yet this time she bumped into the fathers and the husbands of these women. It was their turn to be convinced to have women come to training courses. When she was told that according to religious obligations the place of women is at home, she found theology professors to explain to them that there is no such religious justification. Once she convinced the men, she finally reached the women. She gave them training courses for five days on heath, education, and judicial issues, legal and social rights. Women who used to be afraid of speaking out are now showing the way to those in need of help.
"We gave birth to a lot of children because we were told that making a lot of babies would prevent our men from going to other women,” said Emine Aslan. “I never objected to my husband,” Aslan said, adding, “When I objected to my husband he beat me up, it was first the women in the neighborhood who criticized me for doing so. Women are crueler to women in this country.” Her view is shared by Şükran Bayan who said women are oppressed by women. “When we raise our head to our husbands, other women denounce us,” said Bayan who is 19 years old.
We have been oppressed. I attended the training courses so that other women are not oppressed.” Aslan complained that sending girls to school is deemed dishonorable. “Is it more honorable to sell us to our husbands for some money,” she asked with frustration. “It is no longer enough for me be a leader in my own neighborhood. I will go to school. Sometimes I kid with my husband and tell him I will go to school, become a factory owner and hire him as a worker,” she said.
“I gave birth to 8 children before I was 32. I was not allowed to go outside,” said Şükran Elmas. They would not take her to the hospital when was ill and would beat her for becoming sick. “They did not want my kids to go to school. One of my kids needed a special diet for his sickness. They told me ‘why do you have a special diet. Let him die, you will give birth to another one.’ I can’t remember how many times I tried to commit suicide by drinking rat poison,” said Elmas, who is now 34 years old.
It has not been easy for Elmas to attend a training course. “One person was particularly against my attendance to the training course. I was told that one of my four brothers would kill me and nothing would happen to him even if he was sent to prison. Now I know through the training that I am not desperate against being beaten. I know I have a right to hire a lawyer for free.” Elmas continued her education and she is now a seventh grader. “I used to be ashamed of holding my books. Now I am proud of it. Everyone gets really astonished when I show my student card on public transportation.”
Sümeyye Güç, on the other hand, had to secretly go to the training courses. For her, being beaten was part of being a woman since she saw her father beat her mother all the time. “After the courses I became aware that we are not desperate. I told my mother that she did not have to put up with all these beatings. And I made her break up with my father with whom she had been married formally. Then I registered her to reading and writing courses,” 21 year old Güç said.
She is neither a celebrity nor a prominent politician, but a bodyguard escorts Nahide Opuz at every step, even at the supermarket, to fend off a menace that has proved lethal: her ex-husband. The 39-year-old mother of two is the first Turkish woman to have a government-funded bodyguard after the European Court of Human Rights condemned Turkey in 2009 for failing to protect her and her slain mother.
Before the landmark case reached the judges in Strasbourg, Opuz was repeatedly beaten and survived both a stabbing and an attempt to run her over with a car.
After Turkish authorities repeatedly failed to act on her complaints, her ex-husband killed her mother.
Activists say violence against women in the EU-candidate country has reached an alarming level and point the finger at the judicial authorities and the ruling Islamist-rooted Justice and Development Party, or AKP. In February and March, 52 women were killed by men, according to a tally by BIAnet, a news site focusing on human rights abuses. The figure was at least 217 for last year, and 27 percent of them were killed after asking for a divorce. From 2002 to 2009, the number of women killed in pre-meditated murders rose 14-fold, according to Justice Ministry statistics that do not provide details on the perpetrators and circumstances.
Nearly every day you can read the latest report about a woman being murdered, invariably the murder will be of the most violent nature, be it with shotguns or knives, usually carried out by an estranged or former husband, or family members in a so-called honor killing. In a case earlier this month, a 20-year-old was strangled with her baby . The suspects were her father and brother.
The dramatic increase in killings does not surprise Pinar Ilkaracan of the non-governmental organization, Women for Women's Human Rights.
"The murders are the tip of iceberg; there is a lot of violence against women. There are thousands, tens of thousands of women, who are experiencing violence from their husbands, but they cannot leave home. First of all, what the government should do is increase the number of shelters. There are 26 shelters in 72 provinces of Turkey. This is a scandal by itself, the lowest number in European countries, for example in Germany there are 800 shelters," said Ilkaracan.
Despite the increase in murders, the government rejects such criticisms. It claims it has introduced some of the most far-reaching gender equality legislation in Europe in compliance with EU membership demands. Nimet Cubukcu, former women's minister and now minister of education, is proud of their record.
"The problem in Turkey has reached the level of ‘gendercide,’" said Hülya Gülbahar, a leading women's rights activist. Women have long been victims of violence, including honor killings, in a country where patriarchal traditions persist. But critics argue the problem has been compounded in recent years by the AKP's advocacy of conservative values. "The AKP's conservatism and Islam target the woman's body and sexuality," said Pınar İlkkaracan, a rights campaigner. "What is lacking is the will to eliminate violence against women on the part of the government. They have shown serious resistance" against solving the issue," she said.
Gülbahar also blamed mounting violence on "an intense propaganda that women and men are not equal by creation, and women are therefore responsible for housework and motherhood." Prime Minister – who once called women activists "marginals" – came under fire last year when he said, "men and women cannot be equal" but only "complementary to each other."...
Turkey has full equality on paper, but there is an incredible resistance on the part of the government, including the women's minister, to implement these reforms. Turkey is the country where women's employment is the lowest among OECD countries, the gender gap in education is not decreasing and the number of women in decision-making mechanisms are also decreasing.
Such a grim picture will undoubtedly cause concern in the EU. Women's rights remains one of the key areas of concern over Turkey's membership bid. That concern can only rise on the news of a 14-fold increase in murders of women.
Prime Minister Erdoğan of Turkey announced last month that the "Ministry for Women and Family" will be replaced by a "Ministry of Family and Social Policies," ending explicit focus on women's rights. This is much more than just a name change and signals a reduced emphasis on women's rights, and efforts to promote the rights to non-discrimination and freedom from violence will suffer. Rather than taking the spotlight off women's rights, Turkey needs to take urgent steps to combat endemic violence against women. In the past 10 years since the government has becaome less secular and more Islamic violent deaths of women have risen from less tha 100 a year to nearly 2000.
The existing ministry's mandate was dedicated to working on issue relating to women's rights and the family. The new ministry, however, will deal with issues of concern relating to children, the aged, the disabled, and the families of soldiers who die during active service, as well as family and women's rights. The existing Directorate for the Status of Women will be a department within the ministry.
A Human Rights Watch report issued in May documents brutal and long-lasting violence against women and girls in Turkey by husbands, partners, and family members, and the survivors' struggle to get protection. A study by Turkey's Hacettepe University has shown that about 42 percent of Turkish women experience physical or sexual violence inflicted by a relative at some point in their lives.
Turkey has improved its laws, setting out requirements for shelters for abused women and protection orders. However, gaps in the law and implementation failures by police, prosecutors, judges, and other officials make the protection system unpredictable at best, and at times downright dangerous.
In addition to the high rates of domestic violence in Turkey, other statistics speak to broader gender inequality in the country. In 2010, Turkey ranked 83 on the United Nations Development Programme's global Gender Inequality Index - down six places compared with 2008. Women hold just 9 percent of seats in the national parliament, and only 27 of the country's nearly 3,000 mayors are women.
Women are 27 percent of the paid work force. Only about 19 percent of women are engaged in income-generating work in Turkey, and in the eastern part of the country, the figure is about 10 percent. Illiteracy figures released by the government show great disparities between men and women: 3.8 million of the 4.7 million people who are illiterate are women.
Nearly 50 percent of the women in Turkey’s Eastern city of Şanlıurfa give birth at home. Women do not know that to put henna in the belly button of a baby might be deadly as the baby might get infected. To the contrary they think it is good for the health of the new born. It is a matter of shame to go and see a doctor. Being beaten up is routine. Doing something other than working in the fields is enough to be labeled “bad women.”
Zeynep Şimşek, from Urfa’s Harran University, decided to take the challenge, and women from Şanlıurfa have come to see the head of the University’s Public Health Department as a super hero. As she knew how things worked in one of the most conservative cities in Turkey, Şimşek first tried to convince the men before the women. She first started by training the local headmen. She provided essential information about women's and children's health. She taught them the answers of what to do during pregnancy, how to help women who are victims of domestic violence, where they can go and what their legal rights are. When the local headmen told her, “As men how can we explain all these things to the women? Why don’t you come and tell them yourself?” she caught the opportunity to reach women individually.
Yet this time she bumped into the fathers and the husbands of these women. It was their turn to be convinced to have women come to training courses. When she was told that according to religious obligations the place of women is at home, she found theology professors to explain to them that there is no such religious justification. Once she convinced the men, she finally reached the women. She gave them training courses for five days on heath, education, and judicial issues, legal and social rights. Women who used to be afraid of speaking out are now showing the way to those in need of help.
"We gave birth to a lot of children because we were told that making a lot of babies would prevent our men from going to other women,” said Emine Aslan. “I never objected to my husband,” Aslan said, adding, “When I objected to my husband he beat me up, it was first the women in the neighborhood who criticized me for doing so. Women are crueler to women in this country.” Her view is shared by Şükran Bayan who said women are oppressed by women. “When we raise our head to our husbands, other women denounce us,” said Bayan who is 19 years old.
We have been oppressed. I attended the training courses so that other women are not oppressed.” Aslan complained that sending girls to school is deemed dishonorable. “Is it more honorable to sell us to our husbands for some money,” she asked with frustration. “It is no longer enough for me be a leader in my own neighborhood. I will go to school. Sometimes I kid with my husband and tell him I will go to school, become a factory owner and hire him as a worker,” she said.
“I gave birth to 8 children before I was 32. I was not allowed to go outside,” said Şükran Elmas. They would not take her to the hospital when was ill and would beat her for becoming sick. “They did not want my kids to go to school. One of my kids needed a special diet for his sickness. They told me ‘why do you have a special diet. Let him die, you will give birth to another one.’ I can’t remember how many times I tried to commit suicide by drinking rat poison,” said Elmas, who is now 34 years old.
It has not been easy for Elmas to attend a training course. “One person was particularly against my attendance to the training course. I was told that one of my four brothers would kill me and nothing would happen to him even if he was sent to prison. Now I know through the training that I am not desperate against being beaten. I know I have a right to hire a lawyer for free.” Elmas continued her education and she is now a seventh grader. “I used to be ashamed of holding my books. Now I am proud of it. Everyone gets really astonished when I show my student card on public transportation.”
Sümeyye Güç, on the other hand, had to secretly go to the training courses. For her, being beaten was part of being a woman since she saw her father beat her mother all the time. “After the courses I became aware that we are not desperate. I told my mother that she did not have to put up with all these beatings. And I made her break up with my father with whom she had been married formally. Then I registered her to reading and writing courses,” 21 year old Güç said.
She is neither a celebrity nor a prominent politician, but a bodyguard escorts Nahide Opuz at every step, even at the supermarket, to fend off a menace that has proved lethal: her ex-husband. The 39-year-old mother of two is the first Turkish woman to have a government-funded bodyguard after the European Court of Human Rights condemned Turkey in 2009 for failing to protect her and her slain mother.
Before the landmark case reached the judges in Strasbourg, Opuz was repeatedly beaten and survived both a stabbing and an attempt to run her over with a car.
After Turkish authorities repeatedly failed to act on her complaints, her ex-husband killed her mother.
Activists say violence against women in the EU-candidate country has reached an alarming level and point the finger at the judicial authorities and the ruling Islamist-rooted Justice and Development Party, or AKP. In February and March, 52 women were killed by men, according to a tally by BIAnet, a news site focusing on human rights abuses. The figure was at least 217 for last year, and 27 percent of them were killed after asking for a divorce. From 2002 to 2009, the number of women killed in pre-meditated murders rose 14-fold, according to Justice Ministry statistics that do not provide details on the perpetrators and circumstances.
Nearly every day you can read the latest report about a woman being murdered, invariably the murder will be of the most violent nature, be it with shotguns or knives, usually carried out by an estranged or former husband, or family members in a so-called honor killing. In a case earlier this month, a 20-year-old was strangled with her baby . The suspects were her father and brother.
The dramatic increase in killings does not surprise Pinar Ilkaracan of the non-governmental organization, Women for Women's Human Rights.
"The murders are the tip of iceberg; there is a lot of violence against women. There are thousands, tens of thousands of women, who are experiencing violence from their husbands, but they cannot leave home. First of all, what the government should do is increase the number of shelters. There are 26 shelters in 72 provinces of Turkey. This is a scandal by itself, the lowest number in European countries, for example in Germany there are 800 shelters," said Ilkaracan.
Despite the increase in murders, the government rejects such criticisms. It claims it has introduced some of the most far-reaching gender equality legislation in Europe in compliance with EU membership demands. Nimet Cubukcu, former women's minister and now minister of education, is proud of their record.
"The problem in Turkey has reached the level of ‘gendercide,’" said Hülya Gülbahar, a leading women's rights activist. Women have long been victims of violence, including honor killings, in a country where patriarchal traditions persist. But critics argue the problem has been compounded in recent years by the AKP's advocacy of conservative values. "The AKP's conservatism and Islam target the woman's body and sexuality," said Pınar İlkkaracan, a rights campaigner. "What is lacking is the will to eliminate violence against women on the part of the government. They have shown serious resistance" against solving the issue," she said.
Gülbahar also blamed mounting violence on "an intense propaganda that women and men are not equal by creation, and women are therefore responsible for housework and motherhood." Prime Minister – who once called women activists "marginals" – came under fire last year when he said, "men and women cannot be equal" but only "complementary to each other."...
Turkey has full equality on paper, but there is an incredible resistance on the part of the government, including the women's minister, to implement these reforms. Turkey is the country where women's employment is the lowest among OECD countries, the gender gap in education is not decreasing and the number of women in decision-making mechanisms are also decreasing.
Such a grim picture will undoubtedly cause concern in the EU. Women's rights remains one of the key areas of concern over Turkey's membership bid. That concern can only rise on the news of a 14-fold increase in murders of women.
John 5:24. The criterion for salvation.
I tell you the truth, whoever hears my word and believes him who sent me has eternal life and will not be condemned; he has crossed over from death to life.
Here we have the criterion for salvation. It is not good behavior. It is not a pious life. It is not baptism. It is simply belief. Believe on the Lord Jesus Christ and thou shalt be saved! Cross over from death to life! Simples!
Here we have the criterion for salvation. It is not good behavior. It is not a pious life. It is not baptism. It is simply belief. Believe on the Lord Jesus Christ and thou shalt be saved! Cross over from death to life! Simples!
Dealing with bad behavior like phone hacking
I mentioned Pipril Pete the other day. He was the ex-pharmaceutical rep. who set up a conference organising company that helped me organize my first international conference. We had people from 23 nationalities at the meeting and one of the things I organized at the meeting was for each nationality to tell a national joke. This was the Japanese joke: There was during the war a Japanese Schindler who helped Jews to escape. The irony was that all he did was give his telephone number, 66. In Japanese this sounds like Run-Jew-Run!
No one would volunteer an Irish joke, so I supplied one: Did you hear about the IRA terrorist who tried to blow up a bus? Burnt his lips on the exhaust pipe.
There were Irish people present and i received a sharp missive complaining about the anti-Irish mature of the joke. I had thought it was anti-terrorist rather than anti-Irish, but I realized that much humor is anti-something. It is difficult to avoid offending someone when you start making jokes, whether it be mothers-in-law, women in general, gays, real estators, bankers or even hedgehogs (Why did the hedgehog cross the road? To see his flat mate.)
Psalm one talks about not sitting at the seat of the scornful and if you listen to modern comedians, it is difficult not to. CS Lewis talks about the ambivalent attitude that we have to famous people. Not many of us would resist the temptation to meet a famous person. I once shared the opening of a flower show with the boxer, Frank Bruno. We hear it said again and again that the editor of some newspaper is a rascal, that some politician is a liar, that some official person is a tyrannical Jack-in-office and even dishonest, that someone has treated his wife abominably, that some celebrity leads a most vile and mischievous life. And the general rule in modern society is that no-one refuses to meet any of these people and to behave towards them in the friendliest and most cordial manner. People will even go out of their way to meet them. They will not stop buying the rascally newspaper, thus paying the owner for the lies, the detestable intrusions upon private life and private tragedy, the blasphemies and the pornography, which they profess to condemn wrote Lewis. How it is appropriate to the News of the World phone-hacking scandal.
Lewis (writing more than 50 years ago) asks whether a world in which such 'rascalty' undergoes no social penalty is a healthy one.
How ought we to behave in the presence of very bad people? Especially those who are powerful, prosperous and impenitent. For those who are poor and miserable the Christian has the answer - Christ's attitude to the woman at the well or the woman taken in adultery is our exemplar. But what of the publicans and sinners? They may have been social outcasts to the Pharisees, but they were rich and influential men and it is the Pharisees that Jesus condemns. We cannot compare ourselves to Jesus in his humility, his love, his indifference to social discredit and misrepresentation.
How can we avoid the accusation of priggery if we avoid the popular celebrity? Usually silence is enough. We don't need to get involved. But even if we do not seek out the 'scornful' normal human society brings us into contact. We shall hear vile stories told as funny, the betraying of confidences, gossip behind people's backs, the mocking of things we hold sacred, the lauding of cruelty and all disinterested motives, all heroism, all genuine forgiveness assumed to be phantasmal, idiotic and only believed in by children.
If we do not demur it will be held that 'those Christians' are not so different; their morality is but an act (like Peter round the brazier). Where we must we must disagree. We will doubtless find that we are not alone, and even if in a minority of one, we will sometimes find in the future that we have influenced one of our hearers for the better. As Lewis says, "Even though pedantry is a folly and snobbery a vice, there are circles in which only a man indifferent to all accuracy will escape being called a pedant, and others where manners are so coarse, flashy and shameless that a man of any natural good taste will be called a snob."
No one would volunteer an Irish joke, so I supplied one: Did you hear about the IRA terrorist who tried to blow up a bus? Burnt his lips on the exhaust pipe.
There were Irish people present and i received a sharp missive complaining about the anti-Irish mature of the joke. I had thought it was anti-terrorist rather than anti-Irish, but I realized that much humor is anti-something. It is difficult to avoid offending someone when you start making jokes, whether it be mothers-in-law, women in general, gays, real estators, bankers or even hedgehogs (Why did the hedgehog cross the road? To see his flat mate.)
Psalm one talks about not sitting at the seat of the scornful and if you listen to modern comedians, it is difficult not to. CS Lewis talks about the ambivalent attitude that we have to famous people. Not many of us would resist the temptation to meet a famous person. I once shared the opening of a flower show with the boxer, Frank Bruno. We hear it said again and again that the editor of some newspaper is a rascal, that some politician is a liar, that some official person is a tyrannical Jack-in-office and even dishonest, that someone has treated his wife abominably, that some celebrity leads a most vile and mischievous life. And the general rule in modern society is that no-one refuses to meet any of these people and to behave towards them in the friendliest and most cordial manner. People will even go out of their way to meet them. They will not stop buying the rascally newspaper, thus paying the owner for the lies, the detestable intrusions upon private life and private tragedy, the blasphemies and the pornography, which they profess to condemn wrote Lewis. How it is appropriate to the News of the World phone-hacking scandal.
Lewis (writing more than 50 years ago) asks whether a world in which such 'rascalty' undergoes no social penalty is a healthy one.
How ought we to behave in the presence of very bad people? Especially those who are powerful, prosperous and impenitent. For those who are poor and miserable the Christian has the answer - Christ's attitude to the woman at the well or the woman taken in adultery is our exemplar. But what of the publicans and sinners? They may have been social outcasts to the Pharisees, but they were rich and influential men and it is the Pharisees that Jesus condemns. We cannot compare ourselves to Jesus in his humility, his love, his indifference to social discredit and misrepresentation.
How can we avoid the accusation of priggery if we avoid the popular celebrity? Usually silence is enough. We don't need to get involved. But even if we do not seek out the 'scornful' normal human society brings us into contact. We shall hear vile stories told as funny, the betraying of confidences, gossip behind people's backs, the mocking of things we hold sacred, the lauding of cruelty and all disinterested motives, all heroism, all genuine forgiveness assumed to be phantasmal, idiotic and only believed in by children.
If we do not demur it will be held that 'those Christians' are not so different; their morality is but an act (like Peter round the brazier). Where we must we must disagree. We will doubtless find that we are not alone, and even if in a minority of one, we will sometimes find in the future that we have influenced one of our hearers for the better. As Lewis says, "Even though pedantry is a folly and snobbery a vice, there are circles in which only a man indifferent to all accuracy will escape being called a pedant, and others where manners are so coarse, flashy and shameless that a man of any natural good taste will be called a snob."
Wednesday, July 06, 2011
John 5:23. Jesus in Lord
That all may honor the Son just as they honor the Father. He who does not honor the Son does not honor the Father who sent him.
I am the LORD; that is my name! I will not give my glory to another. So says the Father in Isaiah 42:8. Yet here is Jesus claiming the same honor as the Father. Stressing that he is not a mere ambassador but God himself. Jesus has been making progressively more definitive statements that he is God. There is no middle way; either John is dissembling in a most outrageous way, or Jesus really does claim to be God.
I am the LORD; that is my name! I will not give my glory to another. So says the Father in Isaiah 42:8. Yet here is Jesus claiming the same honor as the Father. Stressing that he is not a mere ambassador but God himself. Jesus has been making progressively more definitive statements that he is God. There is no middle way; either John is dissembling in a most outrageous way, or Jesus really does claim to be God.
Pilgrim's Progress
Yesterday evening we went to the theater for the first time in several years. It was to see The Pilgrim's Progress performed by the Saltmine Trust. It was performed in the modern way with 5 actors a bit of scaffolding and universal costumes and props. But that was fine. The whole audience was elderly and we had all read the book.
I enjoyed it immensely, though being out all that time (three and a half hours) was a bit of a strain.
This is a busy week for Christian things. The Bournemouth and Poole Convention has Frank Retief leading the Bible Readings with Orlando Saer doing the morning studies. Frank preached at our church last Sunday morning. He is the retired Bishop of Cape Town from the Continuing Church of England in South Africa (that's the evangelical lot) and he has preached for us some years ago (probably at least 25). Readers may remember the terrible massacre that occurred in their church (St James) in 1993. (watch the video at http://www.youtube.com/watch?v=ve50OmIg2cE)
Today, I have been relaxing listening to Harry Christophers' Sixteen singing and cleaning a window and this afternoon we visited a couple of garden centers.
Time for a cup of tea.
I enjoyed it immensely, though being out all that time (three and a half hours) was a bit of a strain.
This is a busy week for Christian things. The Bournemouth and Poole Convention has Frank Retief leading the Bible Readings with Orlando Saer doing the morning studies. Frank preached at our church last Sunday morning. He is the retired Bishop of Cape Town from the Continuing Church of England in South Africa (that's the evangelical lot) and he has preached for us some years ago (probably at least 25). Readers may remember the terrible massacre that occurred in their church (St James) in 1993. (watch the video at http://www.youtube.com/watch?v=ve50OmIg2cE)
Today, I have been relaxing listening to Harry Christophers' Sixteen singing and cleaning a window and this afternoon we visited a couple of garden centers.
Time for a cup of tea.
Tuesday, July 05, 2011
APRIL a new target for CLL
APRIL stands for a proliferation inducing ligand. It is a TNF family ligand and has a physiological role in B-cell immunity. It is also believed to have a role in several B-cell malignancies including CLL. High levels of APRIL are correlated with poor prognosis. A group in the Netherlands has developed a pair of monoclonal antibodies that block the binding of APRIL to its receptors.
They have shown that blocking APRIL binding to its receptors has an inhibitory effect on known effects of APRIL both in vitro and in vivo. Importantly, mice treated with APRIL antagonistic antibodies display significant reduction in APRIL serum levels after 2 injections and undetectable levels after 4 weeks of antibody treatment. To demonstrate therapeutic capacity, they extended their study to examine the effect of APRIL antagonism on the survival of lymphoma cells. They confirmed that APRIL binding and stimulation of lymphoma cells, as well as APRIL-induced survival of malignant CLL cells in vitro could be blocked by the antibodies. Their observations confirm the survival benefit APRIL provides to CLL cells, and illustrate the activity of the anti-APRIL antibodies in blocking this.
There has been a recent observation that megakaryocytes, which produce significant amounts of APRIL, are a crucial constituent of the bone marrow niche for plasma cells. Such a selective local production of APRIL may be crucial for the survival of lymphoid malignancies in the bone marrow too. A similar situation appears to exist for CLL where the role of the microenvironment is particularly well established. T-cells and Nurse-Like Cells are described to deliver important survival stimuli. In vitro APRIL, either produced by NLCs or delivered as recombinant proteins can promote survival of CLL cells. These data indicate a significant role for APRIL in the survival of CLL cells in patients and thus support therapeutic intervention with targeting this survival benefit. Similarly, diffuse large B-cell lymphoma patients also appear to have a poor prognosis when their serum level of APRIL is high. Perhaps there will be a role in Richter syndrome.
The toxicity of APRIL antagonistic antibodies should be relatively marginal and thus a valuable option in the selective blocking of lymphoma survival signals and thus the treatment of lymphoma patients. The mouse model for CLL provides evidence that this approach could work. Although this is clearly not a complete model for the disease CLL, they have previously provided compelling evidence that a CLL-like phenotype occurs in this mouse model and the selective B-cell expansion that is reminiscent of CLL is prevented by treatment with the antibody.
They have shown that blocking APRIL binding to its receptors has an inhibitory effect on known effects of APRIL both in vitro and in vivo. Importantly, mice treated with APRIL antagonistic antibodies display significant reduction in APRIL serum levels after 2 injections and undetectable levels after 4 weeks of antibody treatment. To demonstrate therapeutic capacity, they extended their study to examine the effect of APRIL antagonism on the survival of lymphoma cells. They confirmed that APRIL binding and stimulation of lymphoma cells, as well as APRIL-induced survival of malignant CLL cells in vitro could be blocked by the antibodies. Their observations confirm the survival benefit APRIL provides to CLL cells, and illustrate the activity of the anti-APRIL antibodies in blocking this.
There has been a recent observation that megakaryocytes, which produce significant amounts of APRIL, are a crucial constituent of the bone marrow niche for plasma cells. Such a selective local production of APRIL may be crucial for the survival of lymphoid malignancies in the bone marrow too. A similar situation appears to exist for CLL where the role of the microenvironment is particularly well established. T-cells and Nurse-Like Cells are described to deliver important survival stimuli. In vitro APRIL, either produced by NLCs or delivered as recombinant proteins can promote survival of CLL cells. These data indicate a significant role for APRIL in the survival of CLL cells in patients and thus support therapeutic intervention with targeting this survival benefit. Similarly, diffuse large B-cell lymphoma patients also appear to have a poor prognosis when their serum level of APRIL is high. Perhaps there will be a role in Richter syndrome.
The toxicity of APRIL antagonistic antibodies should be relatively marginal and thus a valuable option in the selective blocking of lymphoma survival signals and thus the treatment of lymphoma patients. The mouse model for CLL provides evidence that this approach could work. Although this is clearly not a complete model for the disease CLL, they have previously provided compelling evidence that a CLL-like phenotype occurs in this mouse model and the selective B-cell expansion that is reminiscent of CLL is prevented by treatment with the antibody.
Homes for immigrants
A remarkable Dispatches program on Channel 4 last night. It concerned substandard housing in the UK. We watch a morning BBC program called Homes under the Hammer which shows three properties that come up at auction. They are often semi-derelict but the new owners for the cost of a few thousand pounds can restore them to delightful residences that rent out at between £350 a month.
In the Dispatches program, a landlord was renting out derelict properties at £500 a month in unrestored states and the local authorities were allowing him to get away with it. There is sufficient legislation to send these unscrupulous landlords to prison but the local authorities will not act. The Chief Executive of the company that was investigated had a Muslim name and I'm sorry to say it but the the landlords who do the shoddiest work on Homes under the Hammer are usually Muslims too.
We have had examples of vote-rigging in many northern towns. I am beginning to suspect that graft is to blame for the outrageous state of our housing stock, but it is graft protected by racial and religious sensitivity.
In Southall, West London, another outrage was revealed. Indian landlords are letting out 'sheds' at the bottom of their gardens to illegal immigrants, at the same time breaking the law in trying to legitimize their status. This as well as letting their houses to multi-occupied overcrowding that breaks all health and safety legislation. When challenged by the TV reporter the landlords claimed to be fireproof. More graft?
The people from Shelter, the housing charity, claimed that the problem is due to our poor housing stock, harking back to Mrs Thatcher selling the council houses, but it seems to me that it is more likely due to a vast increase in the population through illegal immigration. May illegals, as we have seen, are paid much less than the minimum wage and consequently pay no tax. I have said that I have no objection to the free movement of labor, but these must be real jobs, not jobs in the 'black' economy.
Holland is reacting to the number of unemployed Poles that have now entered their country and is threatening to deport them, against EU law. It is also threatening to withhold benefits from all non-Dutch speaking residents (again against EU law.
In the Dispatches program, a landlord was renting out derelict properties at £500 a month in unrestored states and the local authorities were allowing him to get away with it. There is sufficient legislation to send these unscrupulous landlords to prison but the local authorities will not act. The Chief Executive of the company that was investigated had a Muslim name and I'm sorry to say it but the the landlords who do the shoddiest work on Homes under the Hammer are usually Muslims too.
We have had examples of vote-rigging in many northern towns. I am beginning to suspect that graft is to blame for the outrageous state of our housing stock, but it is graft protected by racial and religious sensitivity.
In Southall, West London, another outrage was revealed. Indian landlords are letting out 'sheds' at the bottom of their gardens to illegal immigrants, at the same time breaking the law in trying to legitimize their status. This as well as letting their houses to multi-occupied overcrowding that breaks all health and safety legislation. When challenged by the TV reporter the landlords claimed to be fireproof. More graft?
The people from Shelter, the housing charity, claimed that the problem is due to our poor housing stock, harking back to Mrs Thatcher selling the council houses, but it seems to me that it is more likely due to a vast increase in the population through illegal immigration. May illegals, as we have seen, are paid much less than the minimum wage and consequently pay no tax. I have said that I have no objection to the free movement of labor, but these must be real jobs, not jobs in the 'black' economy.
Holland is reacting to the number of unemployed Poles that have now entered their country and is threatening to deport them, against EU law. It is also threatening to withhold benefits from all non-Dutch speaking residents (again against EU law.
More on alemtuzumab
Most people would agree that the alemtuzumab experience has been less that anticipated. We have seen unexpected deaths in some clinical trials and failure of response in patients with bulky disease. A paper in Haematologica addresses this.
They have studied pharmakokinetics in responders and non-responders and lo and behold the non-responders are under-dosed. Maximal concentration of alemtuzumab in responders was 1.69 micrograms per ml and in non-responders was 0.44 micrograms per ml.
I have previously written that the deaths from alemtuzumab, which occurred in an attempt to remove residual disease were caused by giving too large a dose too soon after FCR; I would venture to suggest that failure of bulky disease to respond is due to too small a dose being given. After all the original Lancet paper on Campath had responses in bulky disease.
They have studied pharmakokinetics in responders and non-responders and lo and behold the non-responders are under-dosed. Maximal concentration of alemtuzumab in responders was 1.69 micrograms per ml and in non-responders was 0.44 micrograms per ml.
I have previously written that the deaths from alemtuzumab, which occurred in an attempt to remove residual disease were caused by giving too large a dose too soon after FCR; I would venture to suggest that failure of bulky disease to respond is due to too small a dose being given. After all the original Lancet paper on Campath had responses in bulky disease.
Children and grandchildren
Yesterday we had a visit from our eldest child who brought two of our grandchildren over to see us. Alex, who has just left school to go to college is as tall as me know and is a splendid and polite young man and Aby who is as old in months as Alex is in years. We really have seen very little of her and when Karen left her with us for a job interview she began to cry "Ma!Ma!"
Thankfully she settled in front of children's television after a short while and by the time that Karen returned she was happy and singing to herself and chuckling away. What a joy children and grandchildren are!
All four of our children a great pleasure to us. Karen has film-star looks and a business brain, Richard is formidably bright with a social conscience, Angela is the cleverest person I know and earnest to do good, David is the practical one who can turn his hand to any task and is loved by everyone. All four were keen athletes. All four are intelligent and hard-working. All four are pleasant to be around. All have a sense of fun.
Thankfully she settled in front of children's television after a short while and by the time that Karen returned she was happy and singing to herself and chuckling away. What a joy children and grandchildren are!
All four of our children a great pleasure to us. Karen has film-star looks and a business brain, Richard is formidably bright with a social conscience, Angela is the cleverest person I know and earnest to do good, David is the practical one who can turn his hand to any task and is loved by everyone. All four were keen athletes. All four are intelligent and hard-working. All four are pleasant to be around. All have a sense of fun.
John 5:22. Judgement
Moreover the Father judges no-one, but has entrusted all judgement to the Son.
In the Psalms, judgement is something prayed for and desired; Christians, on the other hand, look forward to judgement with fear and trembling, trusting that the blood of Christ will exonerate them.
The difference is that the Old Testament judgement is a civil judgement as between plaintiff and defendant. " Oh let the nations rejoice and be glad, for thou shalt judge the folk righteously" says Psalm 67. For the Christian, we anticipate our time before the Bar; the criminal court and we know that we are guilty as charged.
Jesus rejected the chance to be a referee. In Luke 12:14 when asked by a man to divide the inheritance between a man and his brother, Jesus replied, “Man, who appointed me a judge or an arbiter between you?”
Through misfortune, slavery, exile and captivity and now Roman oppression the Jews had had the sticky end of the lollipop and were yearning to be treated fairly by a judge who could not be bribed. Our problem is different. Were we to be treated according to our desserts there would be no hope for us. Grace is what we need. We need a judge who has already paid the price of our transgressions - the Son, not the Father.
In the Psalms, judgement is something prayed for and desired; Christians, on the other hand, look forward to judgement with fear and trembling, trusting that the blood of Christ will exonerate them.
The difference is that the Old Testament judgement is a civil judgement as between plaintiff and defendant. " Oh let the nations rejoice and be glad, for thou shalt judge the folk righteously" says Psalm 67. For the Christian, we anticipate our time before the Bar; the criminal court and we know that we are guilty as charged.
Jesus rejected the chance to be a referee. In Luke 12:14 when asked by a man to divide the inheritance between a man and his brother, Jesus replied, “Man, who appointed me a judge or an arbiter between you?”
Through misfortune, slavery, exile and captivity and now Roman oppression the Jews had had the sticky end of the lollipop and were yearning to be treated fairly by a judge who could not be bribed. Our problem is different. Were we to be treated according to our desserts there would be no hope for us. Grace is what we need. We need a judge who has already paid the price of our transgressions - the Son, not the Father.
Monday, July 04, 2011
John 5:21. Raising the dead.
For just as the Father raises the dead and gives them life, even so the Son gives life to whom he is pleased to give it.
Raising the dead was not even common as an attribute of God the Father and many think that this is an eschatological reference. The instances of the dead being raised in Scripture are very few and many of them are at the hand of Jesus. In the last days Jesus will raise some to eternal life but some will be raised to eternal punishment. Today the offer of salvation is made to all men and women.
Raising the dead was not even common as an attribute of God the Father and many think that this is an eschatological reference. The instances of the dead being raised in Scripture are very few and many of them are at the hand of Jesus. In the last days Jesus will raise some to eternal life but some will be raised to eternal punishment. Today the offer of salvation is made to all men and women.
Time spent thinking
My morning starts with time spent thinking. I just listed how many things are on my mind. I started with the BBC drama I watched last evening, "Stolen" about trafficked children from Africa, Russia, Viet Nam and other relatively poor countries. One thing that one of the traffickers said that stuck in my mind was, "we are just supplying a demand." The demand is for cheap labor. That chimed in with something from St Paul, "Before there was a law there was no offence". Whether it is sweat shops in the East End making cheap clothes or sandwiches for London's lunches there are undoubtedly people working for less than the legal minimum wage and many are illegal immigrants and perhaps children. It didn't just start with the minimum wage legislation, but the legislation has revealed how offensive it is.
I have also begun reading CS Lewis' Reflections on the Psalms. He was taking his psalms from the Book of Common Prayer, which translation would be regarded as inaccurate by modern scholars. Nevertheless he has trouble with them, particularly the passages where the psalmist heaps down trouble on his enemies. Having seen the film about the traffickers I have similar feelings about them. I assume that as they are my enemies they are God's enemies too. But I need to put that in context. Are they just businessmen fulfilling a need - the real villains being the consumers; those who use young children as personal slaves and even worse as sex-slaves? Juxtapositioned in my mind is another TV series: The world's strictest parents, in which unruly British teenagers are sent to live with very strict (often Christian) parents, usually in America, and are miraculously tamed in a week. But what often comes out is a deprived child. Last night the girl had a dad with kidney failure who had had three transplants, one from her mother, and the boy who had fathered an illegitimate child had no father-figure at all in his family to be a role model. To understand all is to forgive all. Lewis reminds us that God is not willing that anyone should perish but that all should turn from their wicked ways and live.
I have also been struggling with John's Gospel in that there are so many, probably legitimate, interpretations of the text. Perhaps it was meant to be so. I am using it for devotional readings every day and I am not seeking to provide a comprehensive authoritarian commentary. One thought a day is enough. Our Pastor has started a study in Ecclesiastes on Sunday evenings. I have always loved the book, because it reminds me of my days at University when I tried to find the meaning of life outside of God. I could get no further than 42 (see Hitchhikers Guide).
I then begin to think about stereotypy and immunoglobulin genes in CLL. So much of prognosis in CLL seems to be fore-ordained, being determined by the particular structure of the immunoglobulin gene that powers the tumor line, but as in life events happen and nothing is predictable. To bias our thoughts too much towards 'nurture' or 'nature' is an error. Even identical twins differ at 70 years of age.
The le Carre book I am reading is set in Berlin in the 1970s. Bader-Meinhoff, anarchy, protests, free-love - it all seems so distant now and I never had any sympathy for it. But the need to get out on the street is born of frustration that the politicians are not listening. In the sixties at University, I remember making a speech at the Debating society which bewailed the fact the the 'young leader' that everybody was raving about, Jack Kennedy, was in fact 4 years older than my father. Which brought me to this poem that had it's genesis then though it has been much altered:
Order 451
When the last, time-slipping clock sticks fast,
ratchet-locked and still, and the last rage
rumbles past and yet no screams decry
the cloistered boxing into cocooned cage;
when the sodium painted sky seeps clean
into clear black night and even fairy lights fail;
when the hot, whispered breath is cordoned so tight,
stifled and silenced, blanketed and frail;
when the cold creeps to cover the fire’s faintest spark
and the dark is oppressive, but curbed and defined;
when danger is confined and the limits are quite safe
and they tell us and sell us it’s best left behind;
will you dare to dance lightly on fences and tracks,
face dragons and princes and prisons and pens,
and clamber over palisades and balustrades and pounds
and rip out the restrictions and the rules we need to cleanse?
Anyway that is why I need to settle down for half an hour in the mornings and think.
I have also begun reading CS Lewis' Reflections on the Psalms. He was taking his psalms from the Book of Common Prayer, which translation would be regarded as inaccurate by modern scholars. Nevertheless he has trouble with them, particularly the passages where the psalmist heaps down trouble on his enemies. Having seen the film about the traffickers I have similar feelings about them. I assume that as they are my enemies they are God's enemies too. But I need to put that in context. Are they just businessmen fulfilling a need - the real villains being the consumers; those who use young children as personal slaves and even worse as sex-slaves? Juxtapositioned in my mind is another TV series: The world's strictest parents, in which unruly British teenagers are sent to live with very strict (often Christian) parents, usually in America, and are miraculously tamed in a week. But what often comes out is a deprived child. Last night the girl had a dad with kidney failure who had had three transplants, one from her mother, and the boy who had fathered an illegitimate child had no father-figure at all in his family to be a role model. To understand all is to forgive all. Lewis reminds us that God is not willing that anyone should perish but that all should turn from their wicked ways and live.
I have also been struggling with John's Gospel in that there are so many, probably legitimate, interpretations of the text. Perhaps it was meant to be so. I am using it for devotional readings every day and I am not seeking to provide a comprehensive authoritarian commentary. One thought a day is enough. Our Pastor has started a study in Ecclesiastes on Sunday evenings. I have always loved the book, because it reminds me of my days at University when I tried to find the meaning of life outside of God. I could get no further than 42 (see Hitchhikers Guide).
I then begin to think about stereotypy and immunoglobulin genes in CLL. So much of prognosis in CLL seems to be fore-ordained, being determined by the particular structure of the immunoglobulin gene that powers the tumor line, but as in life events happen and nothing is predictable. To bias our thoughts too much towards 'nurture' or 'nature' is an error. Even identical twins differ at 70 years of age.
The le Carre book I am reading is set in Berlin in the 1970s. Bader-Meinhoff, anarchy, protests, free-love - it all seems so distant now and I never had any sympathy for it. But the need to get out on the street is born of frustration that the politicians are not listening. In the sixties at University, I remember making a speech at the Debating society which bewailed the fact the the 'young leader' that everybody was raving about, Jack Kennedy, was in fact 4 years older than my father. Which brought me to this poem that had it's genesis then though it has been much altered:
Order 451
When the last, time-slipping clock sticks fast,
ratchet-locked and still, and the last rage
rumbles past and yet no screams decry
the cloistered boxing into cocooned cage;
when the sodium painted sky seeps clean
into clear black night and even fairy lights fail;
when the hot, whispered breath is cordoned so tight,
stifled and silenced, blanketed and frail;
when the cold creeps to cover the fire’s faintest spark
and the dark is oppressive, but curbed and defined;
when danger is confined and the limits are quite safe
and they tell us and sell us it’s best left behind;
will you dare to dance lightly on fences and tracks,
face dragons and princes and prisons and pens,
and clamber over palisades and balustrades and pounds
and rip out the restrictions and the rules we need to cleanse?
Anyway that is why I need to settle down for half an hour in the mornings and think.
Sunday, July 03, 2011
John 5:20. God is love
For the Father loves the son and shows him all that he does. Yes, to your amazement he will show him even greater things than these.
The word for love here is 'phileo' not 'agape' as it was in 3:35. It is 'brotherly' or 'family' love. This stresses the relationship between father and son. Here we perceive a mystery that defeats the Muslims. How can one God be a family? Does it not transgress the tenet that there is but one God? Obviously not. When we say that God is love, how could that be before the creation when there was no-one to love? The Father loved the Son and the Son loved the Father and both loved the Holy Spirit.
What were the greater things? What but salvation?
The word for love here is 'phileo' not 'agape' as it was in 3:35. It is 'brotherly' or 'family' love. This stresses the relationship between father and son. Here we perceive a mystery that defeats the Muslims. How can one God be a family? Does it not transgress the tenet that there is but one God? Obviously not. When we say that God is love, how could that be before the creation when there was no-one to love? The Father loved the Son and the Son loved the Father and both loved the Holy Spirit.
What were the greater things? What but salvation?
More on the Greek debts
In last week’s Sunday Times, Matthew Campbell produced a fabulous litany of Athenian parliamentary perks — such as the fact that political parties claim €10 (£9) for every electoral vote in their favour, which they then use as collateral for bank loans, and that their individual MPs are paid 16 monthly salaries a year.
This, however, was as nothing to the perks of the public services detailed by Campbell: bonuses paid to civil servants for washing their hands; other ministries where only half the paid employees actually turn up for work (moonlighting in the meantime) — made almost inevitable by the fact that the vast majority hold jobs from which they constitutionally cannot be fired. In the same spirit, Jason Manolopoulos, the author of Greece’s Odious Debt, wrote last week in The Times: “I know someone who works for the state-owned Hellenic Railways. His workload is two hours a day, he gets 14 months’ salary for a year’s work, yet can still claim for overtime.” Meanwhile, employees in the Greek private sector are among the lowest-paid, and get among the shortest holidays, of any workforce in Europe.
This, however, was as nothing to the perks of the public services detailed by Campbell: bonuses paid to civil servants for washing their hands; other ministries where only half the paid employees actually turn up for work (moonlighting in the meantime) — made almost inevitable by the fact that the vast majority hold jobs from which they constitutionally cannot be fired. In the same spirit, Jason Manolopoulos, the author of Greece’s Odious Debt, wrote last week in The Times: “I know someone who works for the state-owned Hellenic Railways. His workload is two hours a day, he gets 14 months’ salary for a year’s work, yet can still claim for overtime.” Meanwhile, employees in the Greek private sector are among the lowest-paid, and get among the shortest holidays, of any workforce in Europe.
Saturday, July 02, 2011
Benefits of Growing as a Person When Dealing With Cancer
David Haas has asked me to post this article on his behalf on my blog and I am happy to do so.
Benefits of Growing as a Person When Dealing With Cancer
Sometimes we look at life like we are entitled to having it easy and carefree. Have you ever been around anyone who hasn't had to earn or work for what they have? If you have, you have seen that they are often shallow people without dimension. Have you seen someone on the television or been around someone who has faced unimaginable hardship and still has a positive outlook? If you have, you will notice they are strong, wise, and people are drawn to them. When you have a serious diagnosis,such as a terminal cancer like mesothelioma, you will need to make a choice. You will need to choose if you will grow as a person or if the diagnosis will destroy you. Choosing to grow will have many benefits.
BENEFITS OF GROWING AS PERSON WHEN BATTLING CANCER
The National Cancer Institute, which is also known as NCI, can provide you with all kinds of statistics about cancer survival, but who knows where you will fit in. There is no way to predict if someone will exceed their life expectancy or not make it past their first treatment. What is known is that everyone can grow as a person while battling cancer. Here are some keywords that people can grow through while dealing with cancer:
Acceptance
Strength
Peace
Patience
Love
Appreciation
Not everyone grows from a serious diagnosis like cancer or other life threatening illness, but the opportunity is there for everyone. Those who choose the high road often survive longer and enjoy a higher quality of life than those who are eaten up with negativity.
YOU CAN'T CONTROL CANCER, BUT YOU CAN CONTROL YOUR ATTITUDE
controlling your view of your own life with cancer is like choosing to get your head out of a trash can and turning around to look at an awesome sunset. You are still in the same spot, but you choose what to keep your eyes on. Job in the Bible experienced undeserved loss, pain, and illness, yet he didn't curse God. It was the growth during that experience that allowed him to be able to develop a level of acceptance that put him in a position to be blessed abundantly.
Every step towards growth is a victory during your battle with cancer or other life threatening illness. It will bring out hidden strengths and skills that will help you survive.
By: David Haas
Benefits of Growing as a Person When Dealing With Cancer
Sometimes we look at life like we are entitled to having it easy and carefree. Have you ever been around anyone who hasn't had to earn or work for what they have? If you have, you have seen that they are often shallow people without dimension. Have you seen someone on the television or been around someone who has faced unimaginable hardship and still has a positive outlook? If you have, you will notice they are strong, wise, and people are drawn to them. When you have a serious diagnosis,such as a terminal cancer like mesothelioma, you will need to make a choice. You will need to choose if you will grow as a person or if the diagnosis will destroy you. Choosing to grow will have many benefits.
BENEFITS OF GROWING AS PERSON WHEN BATTLING CANCER
The National Cancer Institute, which is also known as NCI, can provide you with all kinds of statistics about cancer survival, but who knows where you will fit in. There is no way to predict if someone will exceed their life expectancy or not make it past their first treatment. What is known is that everyone can grow as a person while battling cancer. Here are some keywords that people can grow through while dealing with cancer:
Acceptance
Strength
Peace
Patience
Love
Appreciation
Not everyone grows from a serious diagnosis like cancer or other life threatening illness, but the opportunity is there for everyone. Those who choose the high road often survive longer and enjoy a higher quality of life than those who are eaten up with negativity.
YOU CAN'T CONTROL CANCER, BUT YOU CAN CONTROL YOUR ATTITUDE
controlling your view of your own life with cancer is like choosing to get your head out of a trash can and turning around to look at an awesome sunset. You are still in the same spot, but you choose what to keep your eyes on. Job in the Bible experienced undeserved loss, pain, and illness, yet he didn't curse God. It was the growth during that experience that allowed him to be able to develop a level of acceptance that put him in a position to be blessed abundantly.
Every step towards growth is a victory during your battle with cancer or other life threatening illness. It will bring out hidden strengths and skills that will help you survive.
By: David Haas
John 5:19. Jesus the Apprentice
Jesus gave them this answer, "I tell you the truth, the son can do nothing by himself; he can do only what he sees his Father doing, because whatever the Father does the son also does."
Although Jesus here claims to be equal to God he does not claim to surpass him. This statement cannot be turned on its head - the Father does what the son does - it is the father who initiates. The relationship between Father and son is perfect; the son follows the Father. Although all the Trinitarian principles are found within John's gospel, and although the word 'trinity' is never used, nevertheless we learn about the relationship of the component persons. Here we have two persons; both one God and the relationship between them as a Father to a son.
We see Jesus following his father's profession perfectly.
Although Jesus here claims to be equal to God he does not claim to surpass him. This statement cannot be turned on its head - the Father does what the son does - it is the father who initiates. The relationship between Father and son is perfect; the son follows the Father. Although all the Trinitarian principles are found within John's gospel, and although the word 'trinity' is never used, nevertheless we learn about the relationship of the component persons. Here we have two persons; both one God and the relationship between them as a Father to a son.
We see Jesus following his father's profession perfectly.
Friday, July 01, 2011
Harry Potter (part 7)
Last night I watched the DVD of Harry Potter and the Deathly Hallows (PART 1). I read the book some time ago and the film follows the book pretty straightforwardly. Every English actor who's ever worked must have got a day's pay from this production since apart from the three children and Ralph Fiennes most appearances are very brief.
The youngsters are now 17 and we get a lot of teenage angst as well as the features of puppy love. We are still at the derring-do stage of the adventure, though the death of the house-elf is a bit moving and we can grieve also over the demise of Dead-Eye. But we had all that with Sirius Black and Dumbledore in previous episodes.
With one film to go, can we evaluate the whole series? As a saga of good versus evil, it doesn't have the sweep of Lord of the Rings. Some have made a fuss about all the sorcery being anti-Christian, but those are just the accoutrement's of the genre.
In the story of the three brothers that explains the Deathly Hallows we begin to see the morality behind the series. Ambition and pride and selfishness are all denigrated; humility is prized. Not very deep then. Betrayal for selfish ends is what haunts them, but Harry is going to have to do something big to defeat Voldemort. I wonder what it could be?
The youngsters are now 17 and we get a lot of teenage angst as well as the features of puppy love. We are still at the derring-do stage of the adventure, though the death of the house-elf is a bit moving and we can grieve also over the demise of Dead-Eye. But we had all that with Sirius Black and Dumbledore in previous episodes.
With one film to go, can we evaluate the whole series? As a saga of good versus evil, it doesn't have the sweep of Lord of the Rings. Some have made a fuss about all the sorcery being anti-Christian, but those are just the accoutrement's of the genre.
In the story of the three brothers that explains the Deathly Hallows we begin to see the morality behind the series. Ambition and pride and selfishness are all denigrated; humility is prized. Not very deep then. Betrayal for selfish ends is what haunts them, but Harry is going to have to do something big to defeat Voldemort. I wonder what it could be?
Harry Christophers
For the past couple of days I have been catching up with my Christmas viewing. Having a PWR recorder on my television I managed to record some rather High Brow programs that I am finally watching, six months late. In particular there were two programs of early choral Christmas music presented by the actor Simon Russel Beale and featuring the choir "Sixteen" whose leader is Harry Christophers. The DVD is available from Amazon and there are many CDs of Harry Christophers' Sixteen. I thoroughly recommend them.
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