A trial and a tribulation

Chapter 18 – visits 6 and 7 to London – a trial starts...

On Monday 7th March, I went to the Cambridge hospital to see my big chief oncologist. I told him that it looked like I was being accepted into the Marsden trial. I mentioned that my left arm had been giving me bouts of pain, perhaps because of the oxaliplatin treatment I had 6 months ago, and asked if I could be prescribed Amitriptyline, which my sister recommended. This was agreed. Then I ran off to do some teaching at the University - a mock select committee hearing, where the students played the role of a government department and various lobbyists, and I played the role of chair of the select committee. That was fun.

On Tuesday 8th March, Ramesh and I picked up my Amitriptyline prescription then took the train to London. At the Marsden I provided a urine sample and signed some final consent forms with one of the doctors in charge of the trial.

On Wednesday 9th March I gave my final lecture on Information Theory in Cambridge.

Then on Thursday 10th March we went down to London again for a 3pm appointment to start the Ramucirumab and Pembrolizumab treatment. There was quite a long wait, because the hospital was short staffed. The treatment got going at about 5pm.

This photo shows the tiny bag of Pembrolizumab – I think this much drug costs about 10,000 pounds.

The only noticeable side-effect of the treatment was that my blood pressure went up a bit.

After being observed for an hour, we were free to return to Cambridge.

Chapter 19 – other ailments

I've had a phlegmy cough for such a long time now, I have lost track of when it started. I started taking antibiotics for the cough about Saturday 5th March. I had a few scintillating scotomas as well in February and early March. Not painful. And I've had a perpetual roaming pain that has wandered around my body: what was at first for a few weeks a spasm in my upper back migrated down and became a severe right rib pain for a week; then it seemed to travel into my left hip, which became superficially tender so that I limped for a few days.

Then we had a delightful three-day collection of meetings: a one-day research-group reunion, and a two-day symposium on "Information Theory, Inference, and Energy" (photo below by jamiegundry.com).

On Tuesday 15th, during the symposium, my hip pain again switched sides and took up residence in my right calf. It felt a lot like a cramp.

On Wednesday morning, given that walking felt quite difficult, I decided that I should ask the medics to check out my calf pain in case it was a deep vein thrombosis (i.e., a clot in a vein in my leg). I phoned the hospital at 8am, and they asked me to see my GP and, if appropriate, get referred back to the hospital. I called the Marsden to let them know what was going on. The GP saw me at 11.20, and reckoned there was a modest chance that I did have a DVT, so he gave me a letter and I cycled to A+E at the hospital. (Walking was difficult but cycling slowly was fine.) We met the Addenbrookes Thrombosis team, who were absolutely wonderful, and at about 1.30pm I was ultrasounded and it turned out that I did have a small DVT.

So, all of a sudden, I'm a different sort of patient, and new medicine is required.

The lovely nurse took my blood samples, I had a talk to the consultant, and then we waited for the results to come back.

The recommended treatment for deep vein thrombosis for a cancer patient is Dalteparin (aka Fragmin, a heparin), which is injected daily.

The nurse showed us how to do the injection. It really hurt!

Then we went home. As I went to bed, we received a phonecall from an out of hours doctor at the hospital who had seen my latest blood results: my "d-dimer" levels were very high, which indicated a thrombosis was likely; he was reassured that I had already been given treatment. How interesting that they can measure these sorts of things from a bit of blood!

A big thank you to our lovely friends who looked after our children repeatedly this day and over the last few weeks!

Chapter 20 – the trial ends?

Today, Thursday 17th March, I had been due to travel down to London for my second Ramucirumab infusion. But the Marsden said that under the experimental protocol, my thrombosis means I can't have Ramucirumab any more. So perhaps my experimental treatment is over. We wait to hear.

I'm staying at home, unable to walk today, but hoping that within a couple of days I'll be on my feet again. Our plan is to go to Wales for a holiday where we hope to enjoy views like this:

Dasher version 5.0 released!

I'm thrilled that a new development team for Dasher is now being led by Ada Majorek, who works for Google in California. Ada has just released Dasher version 5.0, and it is available from https://github.com/ipomoena/dasher/releases.

Version 5.0 has many improvements to practical usability, improving the way that Dasher can interface to real world tasks, such as switching between writing on the computer and having a quick conversation.

I'll update the original Dasher website shortly so that it has pointers to the new release too.

Thank you, Ada, and team!!

After five visits to London hospitals...

Chapter 17 - mulling the lottery of clinical trials
On my first visit to the Marsden hospital near South Kensington, I met a couple of young doctors who explained the trials for which I might be eligible. They didn't exactly line up with what I said in my last blog, and the set on offer actually changed during the day, because doctor 2 added another option to the mix, which doctor 1 hadn't known about; and that extra option is the one I have actually signed up for. After seeing doctors 1 and 2, I met big chief doctor 3, and asked him what he would do in my shoes, and he said he would join the trial that I am now joining. I'll talk about the other option later because it involved some interesting ethical questions, but let's tell you about this recommended trial. It is a trial of two monoclonal antibodies, given together, on days 1 and 8 of a 21-day cycle. The two antibodies are Ramucirumab, which may inhibit blood vessel formation, and thereby sometimes (perhaps in 1 in 5 cases) slows tumour growth; and Pembrolizumab, which may switch on the body's immune response to the cancer (but perhaps only in 1 in 20 or 1 in 10 cases). The data for these two drugs for stomach cancer is quite limited, so all claims of efficacy seem quite uncertain, but the sales pitch from the research doctors was that Ramucirumab is "just as good as the standard second-line treatment" (namely the cytotoxin Paclitaxel, which has a helpful effect in about 1 in 5 cases, which in my view is not great); and that Pembrolizumab offers the chance of remission, albeit an unknown chance, and probably quite small. ("Pem", by the way, is an Anti-PD1, which is a type of monoclonal antibody I had been told by other friends was promising, and I should look out for.)

I am wary of the natural cognitive bias of researchers towards optimism about their research targets. So my gut feeling for asking to join this study was not strong. What made the opportunity more awkward was the "buy immediately while stocks last" pressure: the "Ram+Pem" trial was available internationally, right now, and open to only 6 patients. So if there was any delay, I might not get in!

Tilting me towards joining the trial was the fact that the other trial on offer at the Marsden was a trial that would offer me only "Pem" (not "Ram"), and even then, it would offer only a 50% chance of getting "Pem", thanks to randomisation. In the other branch, the treatment would be the standard second-line cytotoxin, Paclitaxel. So if I didn't get on with joining the Ram+Pem trial, I would definitely be stuck with my only option being a trial that was rated by the experts at least to be inferior to Ram+Pem.

Tilting me in the other direction, against the trial, was the certainty that joining the trial will guzzle up time and energy and will massively constrain my diary, making travel and holidays near-impossible, all in what may prove to be my final six months of life. The trial would involve coming to the hospital roughly twice every week, once for tests, and once for treatment. (Was there any way that some of the tests could simply be done in Cambridge? No, they said.)

I think it is quite comparable to a choice between buying 10,000 lottery tickets per week (so as to get a 1 in 140 chance of winning a jackpot, after a couple of years); or not buying those tickets.

When I discussed this choice with Ramesh, our feeling was that if I was obliged, most weeks, to travel to London on two separate days per week (which is what the doctors indicated would be required) then that would be too much cost. But if the cost were one day-trip to London per week for the rest of my life, then maybe that would be a price worth paying. We made clear to the doctors and the research nurse that we would really really like to not have to travel to London twice in a week.

And we figured, "if we don't like it, we can always withdraw from the trial".

So we decided to sign me up.

And guess what? Ethical rules forbid you from signing up on the same day. So I had to travel home on the train to Cambridge. Then get back on the damn train to London first thing the next morning. And meet the helpful doctor number 1 again. And sign the consent form. Then take the train back to Cambridge. Helpful doctor number 1 did say one nice thing: she said that they had reviewed the timings and they thought that actually it would be possible for me to make just one visit to London per week for the trial. The next step would be for the research nurse to organise for me to be screened, which would involve more trips to London, for a lot of tests. I begged for these screening tests to be combined to minimise my number of trips.

Here endeth the second visit to a London hospital

I was rather disappointed that, even though I'm sure my request for combined tests had been heard and understood, what happened next was a string of single appointments. The first call was about my CT scan. [Because the Marsden's trial required a CT scan even fresher than the very recent one made in Cambridge.] I accepted the appointment, but phoned the research nurse to say, erm, is this CT scan visit going to be combined with anything else? Then I received a letter telling me to come to London for an echocardiogram on another date. I phoned the research nurse again, and she shuffled both appointments and got them to be on a single day, albeit at two hospitals in London separated by more than 1 hour's travel.

Visit number three
As I said, the hospital in Cambridge isn't eligible to carry out tests for the Marsden; but St Anthony's hospital - a private hospital in the outer spiral arm of the galaxy, is. So on Friday 26th February I took the train to London, then a Thameslink train to Sutton, then a bus with a confusing 'next stop' display, which caused me to de-bus one mile early, after which I walked the last mile. The private hospital was very plush. I got echo-cardiogrammed, and the scientist confirmed that I had a heart and that she had no objection to me joining the trial.

Visit number four
A long public-transport journey later, I was at the Marsden for the CT scan. That went smoothly, indeed I was in and out early. And so, back home, to wait for more joined up tests.

The next phonecall I received was from the clinical assessment unit who wanted to schedule my biopsy. The appointment was bang in the middle of my teaching in Cambridge. I asked if the biopsy people could talk to the research people about tweaking the date; the answer was no, this was the only slot that fitted with the required research schedule. So I cancelled and rearranged my teaching, and got on the train to London. An overnight stay was required because they wanted me to show up at 8.30am. As I was getting ready to leave on Tuesday evening, Torrin clung to my leg. I think he was playing, rather than really wanting me "not to go", but the thought of a crying Torrin clinging to my leg and not letting me go stuck with me for the next 24 hours.

Visit number five
Before going to London, I made sure that the Cambridge research gang were aware that I was having a biopsy and that they were given the chance to request some tissue to go to them too. (You might recall that my voluntary gastroscopy-biopsy for Cambridge had failed to yield any satisfactory tissue.) I turned up at the Marsden on time. I was processed steadily by lovely staff (Alex and Greg in particular): cannula in; blood samples taken; answer a checklist; move into a cubicle; change into gown; get wheeled upstairs (by a skilled porter, navigating absurdly narrow corridors); answer a checklist; stare at the wall for 20 minutes; meet the Consultant; sign the consent form; get wheeled into a cold room full of toys; wait there just long enough for my left arm (which has been aching a lot recently) to really start aching. Then the consultant carefully looked with ultrasound in my neck at the target lymph node - I didn't tell you, did I, that the biopsy this time was to be from a lymph node that is enlarged and is therefore "hopefully" cancerous. Its size is still small though - only 9mm by 18mm. And the consultant told me that his bolt gun (I can't remember the correct term) has a throw of 20-25mm! So he was very likely to be chomping adjacent tissue as well as lymph node. Then in came the research nurse to collect the samples, and she told him what size was required, and he shot me slowly four times in the neck - the second impact really gave me a jolt [he said it must have hit a nerve]. Then another long wait in the cold room, then the reverse trolley ride, then a two hour wait accompanied by radio 4 and regular heart check-ups, then I was free to go. Except just before going I thought it was a good idea to phone the research nurse and ask what their plans were and was there anything else I could do for them today?

The research nurse seemed surprised that I hadn't heard: I am due to have visits six and seven on Tuesday and Thursday of next week!

The story goes on. This is way more travelling to London than I hoped, and I am disappointed about the poor communication, but I won't complain at this point. If all goes to plan this next-Thursday visit number 7 will be the start of my experimental Ram+Pem treatment.

Once that is under our belt, I will try to enforce the "only one visit per week" rule.

In other news
As I said, my left arm has been aching a lot (typically for 20 minutes at a time). Also I have been having a perpetual feeling of numbness in my left fingers, especially the tips, and much of the time a similar feeling in my left toes. After talking to my oncologist, I think these are all just long-lasting neuropathies caused by the first cycle of EOX chemotherapy back in August.
At the same time, I have been having awful back trouble. After I helped Torrin learn to ride his bike without stabilisers, I picked up a screaming Eriska, and developed a back spasm that has lasted three weeks now, cunningly moving around the back whenever my masseuse or my physio managed to cure the spasm where it was.
And the last three weeks have been dominated not only by the bad back but also by a non-stop coughy cold.

I'm sorry this feels not a very entertaining chapter.
Let me wrap up with some movie reviews and with the clinical trial anecdote I promised earlier.
The other trial I was offered at the Marsden was a randomised open-label comparison of "Pem" with the standard second line treatment, Paclitaxel, which I could already receive in Cambridge if I wanted it; but if I were in the trial I would be obliged to travel to London every week to have the whatever it was - Pem or Paclitaxel - even if it was in fact Paclitaxel. This felt a silly thing to do - if I got randomised onto the Paclitaxel branch, what would be the point, from my selfish point of view, in travelling to London every week for a treatment I could have got with my lovely Cambridge people? I left this thought unspoken, but one of the staff in London actually voiced exactly this thought for me and said that I would be entitled to leave the study at any point and it would be quite understandable if I were to quit after the randomisation if I were randomised onto the Paclitaxel branch.
I thought it was nice of the staff-member to say this. But would it be ethical to behave in that way? [Statisticians, wanting the trial to be valid, would be horrified at the idea of a patient choosing to leave the trial after the randomisation.] Fortunately I have not had to make this decision, as it looks like I am fully enrolled in a no-randomisation trial.

Movie time!
We have been enjoying some more movies, although we have, among the good ones, chosen a couple of films so awful that we actually stopped watching them, which is not something we often do.
Here are the good ones:

Heist (Gene Hackman) is a film I have seen before but I had forgotten almost all of it. It was a good film. Perhaps an implausible final relationship twist at the end, but lots of nice content along the way. I love heist films.	☆☆☆
The Martian - very well made, and a nice film about science. The one bit I couldn't believe was (in the final act) that Matt Damon would be able to steer his specially-pierced jet-suit without setting himself spinning; and then I couldn't imagine how he could have used his jet to cancel the spin, without producing another unwanted spin.	☆☆☆☆
A nice realistic film was Enough Said, which in spite of being set in Los Angeles was quite watchable. Most of the main characters are female, and the director was female too.	☆☆☆

The uncertainty continues

Chapter 16 – more CT scans, more data

Life is full of uncertainties. For example: Is this the worst cycle-lane pinch-point in Cambridge?

Does anyone in the University of Cambridge administration actually care about this awful junction design? Will our campaign for a safer Huntingdon Road succeed in getting an improved route for cyclists? When will my tumours cause actual trouble?
Data trickle in. We have heard that the University has now (about 3 and a half months after we suggested it) started talking to the land owners about the possibility of buying a thin strip of land to enable the pavement to be widened into a shared-use pavement and off-road cycle path, as indicated in the diagram below.

And I had a CT scan 8 days ago and saw the big chief oncologist today, and he said that the CT scan shows that three lymph nodes in my chest have got significantly bigger (they are all about 10mm wide). He reckons that this probably means the lymph nodes are cancerous, which may not matter too much, because they have room to grow into; but he reckons that there are probably similar secondary tumours elsewhere, and the fact that the lymph nodes have grown in size so soon after I stopped chemotherapy is bad news. Somewhere else, something is probably progressing. When I asked for more information about what 'progress' leads to, he mentioned "six months"; I think this was a worst-case scenario life expectancy.
He thinks I should be offered new treatments. He mentioned two standard treatments using taxanes which are yew tree extracts. One is called docetaxel, and one is paclitaxel. Alternatively I could get experimental treatments. He's going to refer me to the Marsden hospital, where they have trials of (a) a STAT3 inhibitor, which is hoped to interfere with cancer stem cells, and (b) Pembrolizumab, a checkpoint inhibitor. They are all rather unpronounceable and difficult to spell.
I'm disappointed to be back into the chemotherapy system so quickly – I was hoping for a good six months' break or so. And maybe to avoid life being just non-stop chemo, maybe I'll reserve some time for holiday and fun.
Anyway, I'm looking forward to meeting doctors in London; it'll be nice to get more opinions about what should be done with me.

One unexpected finding is that the CT scans show that I have two inferior vena cavas, where most people have only 1.
Other news: Torrin has learned to ride a pedal bike. Eriska has learned how to put duplo pieces together. We've all had upset stomachs and colds, and I'm currently languishing uselessly at home with a frozen-up back, which, frustratingly, is so sensitive that I can't get on and off a bike.
Movies!
We have continued our movie-watching spree, and have seen a few more goodies...

We really enjoyed The Big Short, although it is possible that the equally good documentary Inside Job gives more insight into the explanation of who was to blame (e.g. Goldman-Sachs) and who ended up making loads of money (Goldman-Sachs), thanks to their undeserved bail-out, and who still makes loads of money.	☆☆☆☆☆
We bought the Full Monty style Pride on DVD, about an alliance between gay rights campaigners in London and miners in Wales. This felt a bit predictable in places (especially when Imelda Staunton and her gaggle all overnighted in a gay couple's house, magazines, toys, cackle cackle, ha-ha), but the true-story aspects were striking and memorable.	☆☆☆
Back in the cinema, we thought Trumbo was a fantastic film. A lovely portrayal of blacklisted hollywood during the McCarthy era, doing a good job of portraying different responses to the horrible situation; I especially liked the big argument between Trumbo (the writer) and the big actor who didn't take a stand like Trumbo. And the Goodman Director character was brilliant.	☆☆☆☆☆
When we turn to Netflix, we often struggle to find anything that we want to watch. Perhaps it's just that Netflix has a really bad user interface. I don't know. Anyway, while scraping the bottom of the Netflix barrel, we stumbled on Cowboys and Aliens, which opens as a really well made Western film, then turns into a "what would happen if the flying saucers arrived during the gold rush?" film, with an implausible balance in the fight being achieved by ensuring that the aliens' weapons always fire just a bit behind the fleeing humans, not at them.	☆☆☆
Finally, we watched, again, the lovely Angel's Share.	☆☆☆☆☆

Bye-bye Chemotherapy, Hello TP53!

Chapter 15: starting a new life
There are quite a few developments to report — First, the happiest news: I saw my big chief oncologist on Monday 4 January and we agreed that I am stopping chemotherapy now, having had six cycles of chemotherapy, rather than the full eight cycles that was pencilled in five months ago. Happy happy happy!
Here's the clinical information that underlay this decision. In my latest CT scan, taken on 30th December 2015, the evidence of a secondary tumour in one of the vertebrae of my spine had gone away; my stomach wall looked thin (which is a good thing); and a couple of lymph nodes are potential causes for concern - one of them has plumped up a little since the last scan, and another has become visible that was not visible before. The plump lymph nodes are not necessarily cancerous - they could just be plump because they are busy doing their job. So this seems like a 1-1 draw. I asked my doctor to talk me through the decision to have chemotherapy, which we took five months ago, and to update the decision making to this week's situation. Five months ago I drew, on the basis of what the doctors told me, a quality of life graph like this: showing quality of life versus time without chemotherapy (red) and with (green). The deal, five months ago, was that chemo might reduce quality of life by 20% or so for 6 months, and in return there might be some extension of life, with perhaps a steeper downturn in quality of life at the end; the median extension of life was a remarkably small 2 months, but if you get to be in the lucky right hand half of the distribution [indicated vaguely by dotted lines] you might get a bigger life extension. The doctor recommended trading in the 20% over 6 months in return for the expected life extension. So, this week, I asked the doctor to help me update the graph to the present situation, having completed 6 cycles, and considering whether or not to have another two. He told me that there was considerable uncertainty, no strong evidence of a benefit from cycles 7 and 8, and that other hospitals would recommend only 6 cycles not 8. He said there is good evidence that the bulk of the benefit of chemo comes from the first 3 or 4 cycles. He said it was credible that the benefit of cycles 7 and 8 was no greater than the 6 weeks of life which I'd be devoting to chemo, if I went ahead, and he said that he would be sympathetic if I said 'let's stop', based on my judgement of the expected loss of quality of life. So I said "let's stop" (yippee!). Except first, to put the decision in context, I also asked the doctor to update for me my projected survival curve, which at my time of diagnosis looked something like this, with a central summary of "you might die roughly 12 to 18 months after diagnosis", accompanied by the tail-probability summary: "very unlikely to live more than 2 years after diagnosis". I asked whether the new data and observations over the last five months led him to update these projections. He said, essentially, "no, not yet"; I will have another CT scan in 6 weeks, and that might enable a change of view; and also the fact that I have responded well to the chemo means I am somewhat less likely to be in the left half of the distribution and more likely to be in the right. But my updated prognosis remains "likely to die 12 to 18 months after diagnosis", which means roughly 6 to 12 months from now (with a slim possibility of 18 months). With such small durations on the cards it definitely feels the right decision to stop chemo, to stop being a patient, and get back to feeling fit and having maximum fun as soon as possible. I'd like to thank the Addenbrookes staff for doing a super job of scheduling the CT scan and getting the results analysed in time for my clinic this week; and all the Oncology day unit team for being so lovely during my chemo visits.
The second somewhat shocking development – at least to those who know me – is the acquisition of a new car (also on 4 Jan 2015). This is the first car I have owned since 1991, when, living in LA (where it would of course be against The Constitution not to drive) I owned a tiny red convertible. We have bought a brand new Skoda Fabia. Our main motivation for having a car is so that my wife can learn to drive. Maybe we will go for some road-trips or car-assisted holidays too.
The third piece of news is medical again. As I mentioned in Chapter 10, I enrolled in a research study to attempt to measure my cancer using DNA markers in the blood, I gave research blood every month, and I volunteered to have an extra gastroscopy so that samples of my tumour could be taken away and sequenced. I cycled to the hospital today to hear how the research was going. Surprisingly there was simultaneous good news and bad news: My in-stomach tumour had reduced so much by the time of the gastroscopy that none of the biopsies that were removed from me contained enough tumour tissue to get the required DNA samples! Good news for me and my chemo, but not such good news for the research project. The research team had gone back to my other biopsies that were taken from my peritoneum and that had been fixed in paraffin (which is not good news for the DNA boffins), and pulled out DNA sequences for just 50 genes, including ones that were likely to be mutated in cancers. As I said in Chapter 10, a single gene, called TP53, is mutated in more than 50% of human cancers, and it turns out that TP53 (exon 5) is mutated in mine. All this trouble, just because of one nucleotide! The research team are now thinking of setting up a diagnostic process where I give them a monthly blood sample and they use DNA probes specific to my TP53 mutation to return a month by month measurement that may indicate what my tumours are up to. This seems like a very good deal to me.
The fourth piece of news is an update to our parade of wonderfully-successful film viewings. Courtesy of BBC iplayer we watched the delightful Come as you are, which gets five stars. We also watched the Royal Tenenbaums, which gets two stars.

In closing, here is a data update...
Blood measurements (Haemoglobin, and various white blood counts) before and during six cycles of chemotherapy.

Cycle 6 - and maybe I have had enough of this

Chapter 14 - Pattern spotting
Today is Saturday 2nd January, and Cycle six ended on Wednesday just three days ago. Happily the hospital have given me a week off, which I am looking forward to, before probably restarting with cycle seven next Thursday.
Once you have completed six cycles of chemotherapy, you have enough data to spot some patterns. Of course these may be coincidences.
My main side-effects are, in no particular order:

1. sore spots in my mouth, especially my lips; here I have spotted a pattern: even if I am super careful not to bite my lips, I get sore spots about day 13 of the cycle, and then
   • they get steadily worse and more painful if I'm on the original high dose of chemo; or
   • they get worse for a few days then heal after about 7 days if I'm on the new lower dose.
2. tiredness; here the pattern is that every cycle I am more tired, and tired for longer. In cycle 6 I've had a substantial nap during the day on pretty much every day of the cycle, and even now that I'm a few days into my "week off", I still feel washed out.
3. runny noses and colds; here the pattern is that I got them a lot in the first few high-dose cycles, and I don't seem to be getting them so much in the last two low-dose cycles - hurray! I do still get a runny nose when out in the cold, but it's not bad.

4. Three Torrin-creations in Lego

   the skin of my fingertips falling apart - especially my right finger and thumb, which I use for many important tasks, including taking Lego apart for Torrin. For this side-effect, there is no pattern. The skin is shiny and cracking all the time.

I was given a third CT scan on Wednesday 30th December, to help my doctors decide what to do next. The default is that cycles 7 and 8 will roll along and ruin much of January. I'm hoping that the doctors will have a reason for stopping my chemotherapy now, however, because I have had enough of being tired; I shouldn't complain - I am sure it could be much worse; but I would like to feel well again and have some fun, and I am optimistic that stopping chemotherapy will let me do that.
We have managed to have some fun in the last two weeks, in spite of the chemo. Having got a good handle on my capabilities during cycle 5, we planned a perfectly timed holiday in North Wales in cycle 6, over Christmas, and had great fun on the beach and on a couple of hills, where we enjoyed generous quantities of sun, rain, wind, and sand.
We also enjoyed watching a remarkably good brace of movies.
I'll list here all the movies we've seen in the last month or two, giving star-ratings out of five to highlight the brilliant ones.

The first remarkably good film we saw was Mission Impossible - Rogue Nation, which I thought was possibly the best action movie I've ever seen. After watching it, I re-watched the original Tom Cruise Mission Impossible and found it slow and dull in comparison.	☆☆☆☆☆
Next we saw Bridge of Spies, which was quite a good film, and certainly gave some interesting ideas about how to be a negotiator.	☆☆☆
For our third trip to the big screen we saw Star Wars - the Force Awakens, which was a million times as good as George Lucas's last three Star Warses. I really liked the way they used Han Solo, and the new relationships that they threw us into, and the way that lots more epic personal history has washed by [between episodes six and seven] without being shown. My main complaint is that the film seemed really flickery: I felt I could often see the frame rate	☆☆☆☆☆
Back at home we had a disappointing evening watching The Imitation Game, which is a dud in so many ways - it is criminal how they have replaced Turing's life by fiction. The fiction is far more Hollywood, with ridiculous personal conflicts and drama, such as the notion that Turing was put in charge of the project, overruling his boss; and his boss marching in and dramatically switching off the Bombe while it was in the middle of a computation; and the idea that they were working on code-breaking for ages, including building Bombes, then had the brainwave that one might try to crack messages by guessing what the plaintext was. Awful.	☆
Our next DVD about a Cambridge boffin was Theory of Everything , which was tenderly made and wonderfully acted.	☆☆☆☆
Our next two wonderful successes on DVD were both found by following amazon-recommendations from Ken Loach's lovely film about four young scots, The Angel's Share ,	[☆☆☆☆]
which led us to the absolutely delightful Sunshine on Leith , which is a musical based on the music of the Proclaimers. This film made me cry with happiness not because the three love stories in it were very interesting (they weren't) but because the film is so exuberantly founded on a deep (and perhaps nationalistic?) love of the music of the Proclaimers, which I share. The film is a love-song to the Proclaimers. After we watched this film, everywhere we drove in our borrowed car, we listened to five Proclaimers albums [ Sunshine on Leith , This is the Story , Hit the Highway , Restless Soul , and Life With You ] on continuous-playing shuffle. Glorious!	☆☆☆☆☆
The second amazon-recommendation (based on Angel's Share) was the best film of all, at least in terms of laughs per minute, and perhaps overall: What we did on our holiday - another Scottish film featuring Billy Connolly and three super child actors, and an awesomely funny script highly reminiscent of Parenthood [one of my favourite films of all time] and Little Miss Sunshine .	☆☆☆☆☆
Our sequence of DVD hits continued with the absolutely delightful The Grand Budapest Hotel , which reminded me of the best Harold Lloyd films with its whimsy and speed.	☆☆☆☆☆
Next, An Inspector Calls proved to be a surprisingly gripping watch.	☆☆☆
We tried to continue the joy of viewing The Grand Budapest Hotel by watching the same director's Rushmore but we found it really disappointing. It was somewhat quirky and memorable, but the central love-triangle premise was that the demure teacher-lady-widow, who was both perfect and characterless, was romantically attracted both to a deluded moron of a 15-year old and to a rich 50-year-old jerk. This made no sense, and it was impossible to resonate with any of the characters.	☆
Things picked up with the next DVD: Belle , based on a true story of a mixed-race girl who became a lady in the house of the Lord Chief Justice at the time when the slave trade was going strong, and people of colour were, for upper class snobs, untouchable. Like the Turing film, this film about Belle is heavily fictionalised, but at least the film makers had the honesty to say "based on a true story" in the opening credits.	☆☆☆☆
Last, we watched A Little Chaos , about King Louis 14, his court, and some gardeners making the gardens at Versailles. Alan Rickman does a lovely King, and the scene praised by critics in which the bereaved King has an incognito chat in the garden was indeed nice, but I felt a bit disappointed that we didn't see more of the grandeur and behind the scenes difficulty of the creation of the gardens. The masterpiece garden of Kate Winslet was a disappointment after all the anticipation, given that this was what the whole film was about. And her brainwave, near the beginning of the film, that the fountains in that garden could be fed by perpetually recycled water was most irritating to a physicist, since there was no talk of any pump, only a nonsensical assertion that the "pressure" could be used to recycle the water back to the top.	☆☆

OK, I'll sign out now. Except for completeness, I suppose I should mention the happy news which came out at New Year, that I've just been awarded a knighthood. Many thanks to all my supporters and to my family!

Cycle 5 - getting the hang of chemotherapy

Chapter 13 - Starting to get the hang of chemotherapy [Friday 4 December]
At the start of each cycle, my infusions of "E" and "C" are accompanied by loads of steroids, which produce various side-effects including Hmmm, maybe this isn't a nice topic to open a blog post with... Let's skip over the details and just say that after five rounds of experimentation, I've figured out how to take preemptive Senna and Movicol to manage this one.

In cycle 5, my chemotherapy doses have been reduced for the second time. Apparently this is normal: they start off with doses that they think are likely to be too big for the patient, then watch for side-effects and reduce the doses by roughly 20% at a time. My dose of capecitabine (the toxin I take daily in pill form) was 1300 mg twice daily in cycle 1 and is now 800 mg twice daily.

Whereas in cycle 4 I felt washed out for almost the whole cycle, in cycle 5, I perked up from last Saturday (day 10) to today (day 16), which is great. Ramesh and I spent a day at Torrin's primary school (day 9) helping out with "Maths day". You can see Torrin enjoyed having his parents in school! I went down to London last Wednesday (day 7) for a meeting at Google Deep Mind about using machine learning to enhance climate science and to see Book of Mormon; and then again this Wednesday to give a talk about Why Making Good Energy Policy is Difficult in the House of Lords.

Here is a graph of my haemoglobin and white blood cell measurements. The green and blue lines delimit the "normal range" for each indicator. The brown line at the bottom indicates infusion days that begin each 3-week cycle. The yellow line shows whether I was taking capecitabine.



The interesting features are: (1) the low haemoglobin [June] that kicked off the investigations that led to my cancer being diagnosed; (2) bouts of neutropenia (low white blood counts) at the end of most of the chemo cycles; (3) monocytes are baby neutrophils, so high monocyte counts are a good sign of (temporary) recovery.

What else is going on?

The Huntingdon Road safety campaign #EddingtonSafety has not produced any positive results yet, but we haven't given up hope.

The children have been ill a lot recently; Eriska has followed up a lengthy snotty cold by contracting hand, foot and mouth disease. The doctors tell me to avoid contact if possible, which is sad, because it's nice to cuddle her.

Last night we had an evening out at a new Thai restaurant, Thaikhun, in Cambridge. Yum. Tonight we are planning a night out - thanks very much to Nanny for the babysitting! - to see Bridge of Spies at the cinema.