Benefits and risks of HPV testing in cervical cancer screening


In this issue of The Lancet Oncology, Ronco and colleagues1 clarify the benefits and risks of introducing HPV-DNA testing into cervical cancer screening. In a large randomised trial, adding HPV-DNA testing to cytology doubled the detection of cervical intraepithelial neoplasia grade 3 (CIN3) compared with cytology alone, and (presumably, as a direct consequence) no cancers were observed during follow-up of the HPV-testing group compared with nine cases in the cytology group. As noted by the investigators, the increased detection of CIN3 was primarily due to HPV testing, since cytology added little to the sensitivity of screening when combined with HPV testing. These results are consistent with a trial from India2 that showed decreased cervical cancer incidence and mortality in the HPV-testing group (vs cytology and visual inspection with acetic acid). In Ronco and colleagues’ study, each of the nine women diagnosed with cervical cancers in the cytology group during follow-up had normal cytology at baseline. Four (44%) of these cancers were adenocarcinoma, a proportion four times greater than the expected, confirming that glandular cancers of the cervix are preferentially missed by cervical cytology.

source: Lancet oncology

Dexamethasone in PONV in Lap ccx


Dexamethasone has been reported to reduce postoperative nausea and vomiting (PONV) after laparoscopic cholecystectomy (LC). However, its effects on other surgical outcomes, such as pain and fatigue, have been unclear. We evaluated the efficacy of preoperative dexamethasone for ameliorating postoperative symptoms after LC.
METHODS: In this prospective, double-blind, placebo-controlled study, 210 patients scheduled for elective LC were analyzed after randomization to intravenous dexamethasone (8 mg) or a placebo. All patients underwent standardized procedures for general anesthesia and surgery. Episodes of PONV and the pain and fatigue scores were recorded on a visual analog scale. Analgesic and antiemetic requirements were also recorded.
RESULTS: There were no significant differences between groups with regard to medical or demographic variables. Significantly fewer patients experienced PONV in the dexamethasone group immediately after LC and at 6 and 12 h. The need for ondansetron to relieve PONV was higher in the placebo group (P = 0.001). Patients in the study group reported less postoperative pain during the first 24 h and less fatigue after 6, 12, and 24 h. The need for buprenorphine to relieve intolerable pain was also less in this group (P = 0.009). There were no side effects, and the morbidity was similar in the two groups (6.7 vs. 7.6%).
CONCLUSIONS: The regimen we employed is safe and without apparent side effects. Thus, preoperative dexamethasone can significantly reduce the incidence of PONV, pain and fatigue after elective LC.

Professor Stephen Hawking


Stephen William Hawking was born on 8 January 1942 (300 years after the death of Galileo) in Oxford, England. His parents’ house was in north London, but during the second world war, Oxford was considered a safer place to have babies. When he was eight, his family moved to St. Albans, a town about 20 miles north of London. At the age of eleven, Stephen went to St. Albans School and then on to University College, Oxford; his father’s old college. Stephen wanted to study Mathematics, although his father would have preferred medicine. Mathematics was not available at University College, so he pursued Physics instead. After three years and not very much work, he was awarded a first class honours degree in Natural Science.

Stephen then went on to Cambridge to do research in Cosmology, there being no one working in that area in Oxford at the time. His supervisor was Denis Sciama, although he had hoped to get Fred Hoyle who was working in Cambridge. After gaining his Ph.D. he became first a Research Fellow and later on a Professorial Fellow at Gonville and Caius College. After leaving the Institute of Astronomy in 1973, Stephen came to the Department of Applied Mathematics and Theoretical Physics and since 1979, has held the post of Lucasian Professor of Mathematics. The chair was founded in 1663 with money left in the will of the Reverend Henry Lucas who had been the Member of Parliament for the University. It was first held by Isaac Barrow and then in 1669 by Isaac Newton.

Stephen Hawking has worked on the basic laws which govern the universe. With Roger Penrose he showed that Einstein’s General Theory of Relativity implied space and time would have a beginning in the Big Bang and an end in black holes. These results indicated that it was necessary to unify General Relativity with Quantum Theory, the other great Scientific development of the first half of the 20th Century. One consequence of such a unification that he discovered was that black holes should not be completely black, but rather should emit radiation and eventually evaporate and disappear. Another conjecture is that the universe has no edge or boundary in imaginary time. This would imply that the way the universe began was completely determined by the laws of science.

His many publications include The Large Scale Structure of Spacetime with G F R Ellis, General Relativity: An Einstein Centenary Survey, with W Israel, and 300 Years of Gravity, with W Israel. Stephen Hawking has three popular books published; his best seller A Brief History of Time, Black Holes and Baby Universes and Other Essays, and most recently in 2001, The Universe in a Nutshell.

Professor Hawking has twelve honorary degrees. He was awarded the CBE in 1982, and was made a Companion of Honour in 1989. He is the recipient of many awards, medals and prizes, is a Fellow of The Royal Society and a Member of the US National Academy of Sciences.

Stephen Hawking continues to combine family life (he has three children and one grandchild), and his research into theoretical physics together with an extensive programme of travel and public lectures.

Professor Hawking has given many lectures to the general public. Many of these past lectures have been released in his 1993 book, ‘Black Holes and Baby Universes, and other essays’. Below are some of the more recent public lectures. Included with these lectures is a Glossary of some of the terms used.

Godel and the End of Physics (written in 2002)
“In this talk, I want to ask how far can we go in our search for understanding and knowledge. Will we ever find a complete form of the laws of nature? By a complete form, I mean a set of rules that in principle at least enable us to predict the future to an arbitrary accuracy, knowing the state of the universe at one time. A qualitative understanding of the laws has been the aim of philosophers and scientists, from Aristotle onwards.”

My Life in Physics (written in 2006)
“I did my first degree in Oxford. In my final examination, I was asked about my future plans. I replied, if you give me a first class degree, I will go to Cambridge. If I only get a second, I will stay in Oxford. They gave me a first. I arrived in Cambridge as a graduate student in October 1962.”

The Origin of the Universe
(
written in 2005)
“Why are we here? Where did we come from? The answer generally given was that humans were of comparatively recent origin, because it must have been obvious, even at early times, that the human race was improving in knowledge and technology. So it can’t have been around that long, or it would have progressed even more.”

The Beginning of Time (written in 1996)
“In this lecture, I would like to discuss whether time itself has a beginning, and whether it will have an end. All the evidence seems to indicate, that the universe has not existed forever, but that it had a beginning, about 15 billion years ago. This is probably the most remarkable discovery of modern cosmology. Yet it is now taken for granted. We are not yet certain whether the universe will have an end.”

The Nature of Space and Time
Stephen Hawking and Roger Penrose gave a series of 3 lectures each at the Isaac Newton Institute in Cambridge. The full series is available in a book of the same name. Here we have compiled Stephen’s contribution to the series, as well as the final debate. This is available for download as pdf format or 4 postscript files or (penrose1.pspenrose2.ps penrose3.ps penrose4.ps).

Space and Time Warps (written in 1999)
“In science fiction, space and time warps are a commonplace. They are used for rapid journeys around the galaxy, or for travel through time. But today’s science fiction, is often tomorrow’s science fact. So what are the chances for space and time warps.”

Does God Play Dice (written in 1999)
“This lecture is about whether we can predict the future, or whether it is arbitrary and random. In ancient times, the world must have seemed pretty arbitrary. Disasters such as floods or diseases must have seemed to happen without warning or apparen t reason. Primitive people attributed such natural phenomena, to a pantheon of gods and goddesses, who behaved in a capricious and whimsical way. There was no way to predict what they would do, and the only hope was to win favour by gifts or actions.”

Life in the Universe (
written in 1996)
“In this talk, I would like to speculate a little, on the development of life in the universe, and in particular, the development of intelligent life. I shall take this to include the human race, even though much of its behaviour through out history, has been pretty stupid, and not calculated to aid the survival of the species.”

I am quite often asked: How do you feel about having ALS? The answer is, not a lot. I try to lead as normal a life as possible, and not think about my condition, or regret the things it prevents me from doing, which are not that many.

It was a great shock to me to discover that I had motor neurone disease. I had never been very well co-ordinated physically as a child. I was not good at ball games, and my handwriting was the despair of my teachers. Maybe for this reason, I didn’t care much for sport or physical activities. But things seemed to change when I went to Oxford, at the age of 17. I took up coxing and rowing. I was not Boat Race standard, but I got by at the level of inter-College competition.

In my third year at Oxford, however, I noticed that I seemed to be getting more clumsy, and I fell over once or twice for no apparent reason. But it was not until I was at Cambridge, in the following year, that my father noticed, and took me to the family doctor. He referred me to a specialist, and shortly after my 21st birthday, I went into hospital for tests. I was in for two weeks, during which I had a wide variety of tests. They took a muscle sample from my arm, stuck electrodes into me, and injected some radio opaque fluid into my spine, and watched it going up and down with x-rays, as they tilted the bed. After all that, they didn’t tell me what I had, except that it was not multiple sclerosis, and that I was an a-typical case. I gathered, however, that they expected it to continue to get worse, and that there was nothing they could do, except give me vitamins. I could see that they didn’t expect them to have much effect. I didn’t feel like asking for more details, because they were obviously bad.

The realisation that I had an incurable disease, that was likely to kill me in a few years, was a bit of a shock. How could something like that happen to me? Why should I be cut off like this? However, while I had been in hospital, I had seen a boy I vaguely knew die of leukaemia, in the bed opposite me. It had not been a pretty sight. Clearly there were people who were worse off than me. At least my condition didn’t make me feel sick. Whenever I feel inclined to be sorry for myself I remember that boy.

Not knowing what was going to happen to me, or how rapidly the disease would progress, I was at a loose end. The doctors told me to go back to Cambridge and carry on with the research I had just started in general relativity and cosmology. But I was not making much progress, because I didn’t have much mathematical background. And, anyway, I might not live long enough to finish my PhD. I felt somewhat of a tragic character. I took to listening to Wagner, but reports in magazine articles that I drank heavily are an exaggeration. The trouble is once one article said it, other articles copied it, because it made a good story. People believe that anything that has appeared in print so many times must be true.

My dreams at that time were rather disturbed. Before my condition had been diagnosed, I had been very bored with life. There had not seemed to be anything worth doing. But shortly after I came out of hospital, I dreamt that I was going to be executed. I suddenly realised that there were a lot of worthwhile things I could do if I were reprieved. Another dream, that I had several times, was that I would sacrifice my life to save others. After all, if I were going to die anyway, it might as well do some good. But I didn’t die. In fact, although there was a cloud hanging over my future, I found, to my surprise, that I was enjoying life in the present more than before. I began to make progress with my research, and I got engaged to a girl called Jane Wilde, whom I had met just about the time my condition was diagnosed. That engagement changed my life. It gave me something to live for. But it also meant that I had to get a job if we were to get married. I therefore applied for a research fellowship at Gonville and Caius (pronounced Keys) college, Cambridge. To my great surprise, I got a fellowship, and we got married a few months later.

The fellowship at Caius took care of my immediate employment problem. I was lucky to have chosen to work in theoretical physics, because that was one of the few areas in which my condition would not be a serious handicap. And I was fortunate that my scientific reputation increased, at the same time that my disability got worse. This meant that people were prepared to offer me a sequence of positions in which I only had to do research, without having to lecture.

We were also fortunate in housing. When we were married, Jane was still an undergraduate at Westfield College in London, so she had to go up to London during the week. This meant that we had to find somewhere I could manage on my own, and which was central, because I could not walk far. I asked the College if they could help, but was told by the then Bursar: it is College policy not to help Fellows with housing. We therefore put our name down to rent one of a group of new flats that were being built in the market place. (Years later, I discovered that those flats were actually owned by the College, but they didn’t tell me that.) However, when we returned to Cambridge from a visit to America after the marriage, we found that the flats were not ready. As a great concession, the Bursar said we could have a room in a hostel for graduate students. He said, “We normally charge 12 shillings and 6 pence a night for this room. However, as there will be two of you in the room, we will charge 25 shillings.” We stayed there only three nights. Then we found a small house about 100 yards from my university department. It belonged to another College, who had let it to one of its fellows. However he had moved out to a house he had bought in the suburbs. He sub-let the house to us for the remaining three months of his lease. During those three months, we found that another house in the same road was standing empty. A neighbour summoned the owner from Dorset, and told her that it was a scandal that her house should be empty, when young people were looking for accommodation. So she let the house to us. After we had lived there for a few years, we wanted to buy the house, and do it up. So we asked my College for a mortgage. However, the College did a survey, and decided it was not a good risk. In the end we got a mortgage from a building society, and my parents gave us the money to do it up. We lived there for another four years, but it became too difficult for me to manage the stairs. By this time, the College appreciated me rather more, and there was a different Bursar. They therefore offered us a ground floor flat in a house that they owned. This suited me very well, because it had large rooms and wide doors. It was sufficiently central that I could get to my University department, or the College, in my electric wheel chair. It was also nice for our three children, because it was surrounded by garden, which was looked after by the College gardeners.

Up to 1974, I was able to feed myself, and get in and out of bed. Jane managed to help me, and bring up the children, without outside help. However, things were getting more difficult, so we took to having one of my research students living with us. In return for free accommodation, and a lot of my attention, they helped me get up and go to bed. In 1980, we changed to a system of community and private nurses, who came in for an hour or two in the morning and evening. This lasted until I caught pneumonia in 1985. I had to have a tracheotomy operation. After this, I had to have 24 hour nursing care. This was made possible by grants from several foundations.

Before the operation, my speech had been getting more slurred, so that only a few people who knew me well, could understand me. But at least I could communicate. I wrote scientific papers by dictating to a secretary, and I gave seminars through an interpreter, who repeated my words more clearly. However, the tracheotomy operation removed my ability to speak altogether. For a time, the only way I could communicate was to spell out words letter by letter, by raising my eyebrows when someone pointed to the right letter on a spelling card. It is pretty difficult to carry on a conversation like that, let alone write a scientific paper. However, a computer expert in California, called Walt Woltosz, heard of my plight. He sent me a computer program he had written, called Equalizer. This allowed me to select words from a series of menus on the screen, by pressing a switch in my hand. The program could also be controlled by a switch, operated by head or eye movement. When I have built up what I want to say, I can send it to a speech synthesizer. At first, I just ran the Equalizer program on a desk top computer.

However David Mason, of Cambridge Adaptive Communication, fitted a small portable computer and a speech synthesizer to my wheel chair. This system allowed me to communicate much better than I could before. I can manage up to 15 words a minute. I can either speak what I have written, or save it to disk. I can then print it out, or call it back and speak it sentence by sentence. Using this system, I have written a book, and dozens of scientific papers. I have also given many scientific and popular talks. They have all been well received. I think that is in a large part due to the quality of the speech synthesiser, which is made by Speech Plus. One’s voice is very important. If you have a slurred voice, people are likely to treat you as mentally deficient: Does he take sugar? This synthesiser is by far the best I have heard, because it varies the intonation, and doesn’t speak like a Dalek. The only trouble is that it gives me an American accent.

I have had motor neurone disease for practically all my adult life. Yet it has not prevented me from having a very attractive family, and being successful in my work. This is thanks to the help I have received from Jane, my children, and a large number of other people and organisations. I have been lucky, that my condition has progressed more slowly than is often the case. But it shows that one need not lose hope.

Communication system

I communicate with a computer system. I have always used IBM compatible computers, on my wheel chair. They run from batteries under the wheel chair, although an internal battery will keep the computer running for an hour if necessary. The screen is mounted on the arm of the wheel chair where I can see it, more recent systems have the whole computer in a box on this arm. The original systems were put together for me by David Mason, of Cambridge Adaptive Communications. This company manufacture and supply a variety of products to help people with communication problems express themselves. Recently, Intel engineers designed a new computer for me powered by a Pentium II processor, which I now use.

On the computer, I run a program called Equalizer™, written by a company called Words Plus inc. A cursor moves across the upper part of the screen. I can stop it by pressing a switch in my hand. This switch is my only interface with the computer. In this way I can select words, which are printed on the lower part of the screen. When I have built up a sentence, I can send it to a speech synthesizer. I use a separate synthesizer, made by Speech+. It is the best I have heard, though it gives me an accent that has been described variously as Scandinavian, American or Scottish. I also can use Windows 98 through an interface called EZ Keys, again made by Words Plus. I am able to control the mouse with the switch through cleverly selected process from a small box shown on the desktop. I can also write text using similar menu’s to those in Equalizer.

I can save what I write to disk. I write papers using a formatting program called TEX. I can write equations in words, and the program translates them into symbols, and prints them out on paper in the appropriate type. I can also give lectures. I write the lecture beforehand, and save it on disk. I can then send it to the speech synthesiser, a sentence at a time. It works quite well, and I can try out the lecture, and polish it, before I give it.

Stephen Hawking

Recent Improvements

Professor Hawking is determined that he is able to keep up with the recent improvements in computer and communication technology. Below are some of the recent improvements, which have been carried out on the system within the last 12 months.

In non-wireless areas, Intel manage a 3G account for us so that Professor Hawking is able to use the internet from anywhere in the world, via a PCMCIA 3G card.

The computer has been replaced about once per year; it is currently (Jan 2009) running on a Lenovo Thinkpad T60 and the next model will have an X61 at its heart.

Upgrade to Windows XP (in around 2001)
The computer is running on Windows XP. For many years it has been impossible to upgrade beyond Windows’98, because Professor Hawking’s favourite speech software, Equalizer by Words-Plus, was made in 1986, and was designed to run only on DOS based operating systems. However, Intel has kindly funded the conversion of the software to XP. This involved Words-Plus re-writing the whole program for today’s operating system.

Power
Due to Professor Hawking’s active lifestyle, it is impossible to power his chair computer via the mains as he is never in one place long enough to make this practical. Thus the laptop needs to be powered by the wheelchair batteries, which are similar to car batteries, in the back of the chair.

Keep talking
It is essential that Stephen is able to make use of a telephone. He is able to use Voice over IP, or connect his chair computer directly to a telephone socket. The process works by sending digital commands from his computer instructing the phone system to dial a number, answer the phone or hang up at the end of a call.

Who’s got the remote?
Stephen has a universally programmable infra-red remote control attached directly to his computer system. This enables him to operate many of the electronic items in his home, such as televisions, video recorders and music centres. He also has a radio control device which enables him to open doors and operate lights throughout his home. He is now also able to operate doors within his workplace. With the opening of the newly built Centre for Mathematical Sciences, he will be able to get about the building virtually unassisted.

Professor Hawking floating in zero gravity

Professor Hawking experienced weightlessness for the first time on April 26, 2007

source: official web site of Prof Hawking

http://www.hawking.org.uk/

Angiotensin-receptor blockers and cancer: urgent regulatory review needed


The meta-analysis, published today in The Lancet Oncology, by Sipahi and colleagues1 is disturbing and provocative, raising crucial drug safety questions for practitioners and the regulatory community. Are angiotensin-receptor blockers (ARBs) associated with increased risk of incident malignancies? Should we be concerned about all ARBs or a single drug, telmisartan? How can this uncertainty best be resolved? What actions should practitioners take while this concern undergoes further examination and analysis?

source: Lancet oncology