Cryptic Diversions

The first cryptic crossword clue is taken from the novel A Week in December by Sebastian Faulks:

          Butcher has ox tongue (5)

The second comes from one of Tim Morey's recent puzzles in The Week:

          It can be shuffled (7)

And these two are winning entries in a clueing contest devised by The Telegraph's puzzles editor, Chris Lancaster:

          Play this for 14 or more (8)

          Bird's very large eggs withheld from Putin's comrade (7)

The first two involve anagrams flagged up by the words "butcher" and "shuffled", the second being in &lit format. The third needs lateral thinking and some knowledge of a well-known board game. The final clue is a combination of charade and deletion and calls for some erudition: an abbreviation used by purveyors of large clothing, the Latin word for "eggs". and the Russian word for "comrade".

Covid Vaccine Update

The Oxford team mentioned in the Front-runners post below have started clinical trials and plan to test 6,000 people by the end of May.They are also preparing for large scale production in case their vaccine proves effective.

Epidemics Animated

Grant Sanderson's YouTube Channel 3Blue1Brown has the most wonderful animations of things mathematical, full of insight and thoughtful intelligence. He has devoted  a recent video to a striking visual simulation of how models predict the transmission of disease in epidemics. If you would like to understand better what our Government means by the phrase "guided by the science" in their daily briefings, click on this link.  It's essential viewing and I strongly recommend it  (and it contains no equations, I promise).

More Shakespeare streamed

Royal Shakespeare Company, Stratford upon Avon

CULTURE IN QUARANTINE

We have partnered with the BBC to bring six of our shows to television audiences through BBC iPlayer and BBC4.

Macbeth (2018), directed by Polly Findlay with Christopher Eccleston and Niamh Cusack

Hamlet (2016), directed by Simon Godwin with Paapa Essiedu

Romeo and Juliet (2018), directed by our Deputy Artistic Director Erica Whyman

Much Ado About Nothing (Love's Labour's Won) (2014), directed by Christopher Luscombe

Othello (2015), directed by Iqbal Khan with Hugh Quarshie and Lucian Msamati

The Merchant of Venice (2015), directed by Polly Findlay

FIND OUT MORE

WATCH ON IPLAYER

Reducing the DOTS for Infectious Diseases

To measure of how fast an infectious disease is spreading, you need to know the Reproduction Number. This is the average number of people someone with the disease will infect during the course of their illness. 

• If the reproduction rate is bigger than 1 the disease will spread, and the larger it is, the faster it will spread
• If the reproduction rate is less than 1, the disease will die out, and the smaller it is, the quicker it will disappear.

The value of the reproduction rate is determined by four quantities, the DOTS:

Duration. The number of days someone with the disease is infectious

Opportunity. The average number of close contacts a typical person has each day.

Transmission, The proportion of contacts that lead to the infection being passed on.

Susceptibility. The proportion of the population without immunity.

Reducing any of these four numbers will slow the spread of the pathogen. If the reproduction rate stays below 1,  the disease will eventually go away.

How can we reduce the DOTS for the novel coronavirus?

• We can’t change the duration of SARS-CoV-2 because that is an intrinsic property of the disease when it is allowed to run its course without intervention, and we have no proven treatment at the moment.
• At the beginning of the outbreak, the susceptibility was 100% because no one had had covid-19 before, and we can’t actively change it until we get a safe and effective vaccine. However, it is expected that people who have recovered from the disease will have antibodies produced by their immune systems, which should afford them some protection against reinfection; but at what level and for how long is still unknown.

That leaves opportunity and transmission.

• We can make a big reduction on the opportunity by keeping people at home and quarantining those that show symptoms or have underlying health problems. The experience in Wuhan strikingly showed this: before the outbreak the average daily number of contacts was 15. This number dropped to 2 during the strict lockdown and the reproduction rate fell to 0.6. Consequently the disease died out.
• Social distancing also has a big effect on reducing the transmission rate. Washing hands and surfaces, covering mouth and nose with a tissue when coughing and sneezing, and probably wearing masks also help to minimise it.

Other issues that need to be taken into account are: silent spreaders (those with no symptoms who are nevertheless passing on the infection in all innocence); super-spreaders (those with a high viral load who, because of their work or lifestyle, have very many contacts); the different immune responses of men and women, young and old; genetic mutations of the virus, which have already been identified and used to show the convoluted journeys different strains have made around the world.

Readers seeking more of the details behind this post might be interested in the timely book The Rules of Contagion by Adam Kucharski, published on February 13th. He must either have had inside information or a good fortune-teller.

Frontrunners in the Race for a Coronavirus Vaccine

Two early candidates for vaccines to protect against Covid-19 are already undergoing animal trials on ferrets at the Australian Centre for Disease Preparedness, a high security laboratory in Geelong, Victoria. They both employ innovative approaches that depend only on knowing the genetic code of the novel corona virus (SARS-CoV-2), and this was published by Chinese scientists in early January. The fact they didn’t need quantities of the actual virus gave them a head start.  These two candidates were chosen by the Coalition for Epidemic Preparedness Innovations (CEPI), who are funding the Australian work and had already set up the pipeline before the covid-19 outbreak  began. The two teams leading the charge are:

The Oxford University Vaccine Group and Oxford's Jenner Institute are using a harmless non-replicating chimpanzee adenovirus to carry the genetic code for a protein found on the surface of the coronavirus (see picture).

Immune responses from other coronavirus studies suggest that these club-shaped spikes are a good target for a vaccine. After vaccination, the adenovirus enters our cells and starts to produce the surface-spike protein of the coronavirus, which then primes our immune systems to attack the coronavirus if it later infects our bodies. (Chimpanzee adenoviral vectors are a very well-studied vaccine type and have been used safely on thousands of subjects, from new-born babies to 90-year-olds, in vaccines targeting over 10 different diseases.)

Inovio is an American bio-technology firm specialising in DNA-based immunotherapy. The human cell has many amazing functions and in particular is a protein factory for making and maintaining our body parts. Their vaccine magically inserts a piece of the coronavirus DNA directly into the human cells in such a way that it can borrow the cell’s machinery to make the viral protein that will prepare the immune system to destroy any invasion by the actual virus before it can take hold. This is a completely novel approach and has not be used in a vaccine before.

Why Ferrets? In 2003, when a different coronavirus (SARS) struck, a team at the Scripps Research Institute in Florida discovered that it was getting into human cells by targeting a specific receptor called ACE2 on certain cells in the lining of the lungs and in other vital organs. It turns out these receptors in ferrets’ lungs are very similar to those in humans and make the ferret an ideal ‘guinea-pig’ to study the progression of covid-19 and the effectiveness of the vaccine. The first cohorts of ferrets were infected and separately inoculated in March and preliminary results should be available by the end of April. Another group of ferrets will receive a second booster dose of the vaccine before being infected. A full assessment of the trials will be made available to the two teams in the UK and the USA by mid-July. Meanwhile, both teams have started the first phase of clinical trials on humans.

Clinical trials. These typically have three phases:

Phase 1. A small group (around 40--50)  of brave people are shielded from exposure to the virus and injected with the vaccine to see if it has harmful effects. This is a safety test, not a test of efficacy. 

Phase 2. A much larger group of people from the general population who would be naturally exposed to the virus are divided into two groups. One half are injected with the vaccine, the other half with water; neither those carrying out the trial nor those participating know which group they belong to (a so-called double-blind trial). After a sufficient time elapses for exposure to have occurred, the levels of infection from the two groups are compared. Ideally the trials should be continued for a much longer time to find out how long immunity, if any, is conferred by the vaccine.

Phase 3. When the safety and the efficacy has been confirmed, the programme of large scale vaccinations is rolled out.

This project is a striking example of the power of international cooperation. If Inovio is successful, it could even go a small way to making America Great again!

Updates

1. CEPI receives its funding from philanthropic (e.g.Gates Foundation), institutional (e.g. Wellcome Trust) and international sources (Japan, Norway, Germany, Australia, Belgium and Canada). In March 2020, the British government pledged £210m. specifically to focus on a SARS-CoV-2 vaccine, making Britain CEPI's largest individual donor.

2. Ferrets now have a rival species for testing. When a Hong Kong team recently infected 8 hamsters with SARS-CoV-2, high levels of the virus were found in the hamsters’ lungs and intestines, tissues studded with the virus’ target  protein: angiotensin-converting enzyme 2 (ACE2). 

3. Two of the world's largest vaccine manufacturers, GlaxoSmithKline and Sanofi, are joining forces to develop a new vaccine to prevent Covid-19.

Post deleted

Apologies to my loyal followers -- see here. I was advised that my parody might be believed,

National Theatre Streaming

Uncontrolled guffaws have recently been heard from our sitting room, thanks to our National Theatre's generous offer of free Thursday evening streaming of a selection of their shows during this time of coronavirus; the first show was a beautifully filmed version of their stage production of One Man, Two Guvnors. Each stream will be available on YouTube until the following Thursday.

For a long time I made the pretence of not enjoying farce or slapstick humour - over-exposure to pantos as a child perhaps. (Why did Widow-Twanky always end up with wallpaper and a bucket of paste?) But after watching One Man, I now realise I am as much of sucker for a good farce as I am for rom-coms. I probably began to change my mind after I saw Michael Frayn's Noises Off - I had always admired him from the early days when he wrote a humorous column every Tuesday in the Manchester Guardian (as it then was). I now appreciate that, for cinematic comedy of that kind, Buster Keaton and Charlie Chaplin were the geniuses of their day. Another belly-laugh-inducing example of the genre is The Play That Goes Wrong put on by Mischief Theatre, performances of which we can only hope will continue at the Duchess Theatre in London when normal life resumes. 

Web resul

Mind-Benders for the Quarantined

The Museum of Mathematics in New York ihas set up a weekly challenge for the house-bound mind. Each Sunday an elegant puzzle from the collection of the master puzzler, Peter Winkler, arrives in your inbox. It is followed by a subtle hint on Tuesday, a serious push on Thursday and the full solution on Saturday. 

In the past two weeks. I have been asked to help Oskar the ostrich test the hardness of his eggs by dropping them from ever higher floors of the Empire State Building, and to find short cuts for someone in a hurry who has forgotten the number of their faulty combination lock. Sign up, stay sharp and start puzzling.

Covid-19 Mobile Apps for the United Kingdom

COVID Symptom Tracker. Developed by King's College London and fully operational now.

Take 1-minute to self-report daily, even if you are well and help our scientists identify:

• High-risk areas in the UK

• Who is most at risk, by better understanding symptoms linked to underlying health conditions

• How fast the virus is spreading in your area

Download here 

 

     

The NHS Contact Tracker. 

This ambitious app is under development by the National Health Service Digital Team NHSX. It is hoped it will be ready to launch in 4 -- 6 weeks. It will track infected cases and alert those who have been in close contact with them so that they can self-isolate. It will slow the transmission rate and work better as the pandemic comes under control. To be most effective it will need a high level of national participation.