Tuesday, December 16, 2014

Supporting the Austrian Pledge on Nuclear Weapons abolition

Daniela Varano of the International Campaign toAbolish Nuclear Weapons writes:

"We have some great news from Vienna. After 44 states called for a prohibition on nuclear weapons at the Third Conference on the humanitarian impacts of nuclear weapons, Austria delivered an "Austrian Pledge" at the closing of the meeting.

Austria called on all states to "fill the legal gap for the prohibition and elimination of nuclear weapons" and pledged to "cooperate with all stakeholders to achieve this goal".

This is an extremely exciting development for our campaign, and now it's time for all states committed to nuclear disarmament to join the Austrian pledge to work towards filling that legal gap by negotiating a treaty banning nuclear weapons. We want Austria to know we appreciate their courage and will push other governments to do the same".


They ask for letters of encouragement. Here is mine, sent today:


Dear Foreign Minister Kurz,

I am writing to say how much I welcome your country’s leadership in hosting the Vienna Conference on the Humanitarian Impact of Nuclear  Weapons.

The discussions in Vienna give us great hope for the essential next step - starting work on negotiations to ban them all.  Austria’s firm pledge to support this is courageous and inspiring.  It would start with all those states ready to take part. But even this will put tremendous political pressure on those few states who are holding the rest of us hostage with their insistence that nuclear weapons actually defend them.  Austria is now in an excellent position to give the lead we need.

The matter will of course be highly contentious. Nuclear Weapons States (NWS) have a huge investment in the status quo, including financial, emotional and political motivations. They will defend their position tenaciously, and I would like to anticipate the arguments that you will meet. I apologise that this letter is rather long.

The Insurance Policy Argument
First, they will argue that posession of Nuclear Weapons of Mass Destruction (NWMD) constitutes an insurance policy.This is a powerful argument at the emotional level; after all, who would like to go into an uncertain future without insurance of some kind? Insurance is good and sensible.

But does the insurance metaphor stand up to scrutiny?

With insurance, we pay a certain amount of money regularly into a common fund. The fund increases, and if in time something untoward happens to one of those paying into the fund, that person receives an amount of money from the fund which enables them to make good the loss that they have sustained.

It is impossible to see how this analogy obtains with NWMD. The NWS does make payments for their weapons, but it is not a common fund in the sense that any number of other nations pay into it. It is only a fund for the NWS itself. If a nuclear attack is made on an NWS, the state does not get an amount of money to make good the damage done. Instead, all they get is the dubious satisfaction that the person or persons who launched the nuclear attack will suffer just as much death, injury, burns, destruction, disruption, disease, misery and cancer as the first state have suffered. So NWMD posession is in no way analogous to an insurance policy, and in describing it as such, heads of NWS are trying to delude themselves and their audience.

The logic of infinite destruction and greater than zero probability
We should bring clear and simple logic to a debate that is prone to become confused and emotional.

Let us start with a simple general proposition that is unassailable:

If the consequences of the failure of a system would be infinitely destructive to civilisation, it is reasonable to use that system if, and only if, the probability of its failure are zero.

Applying that statement to the NWMD case, the argument is that there is a greater than zero chance of nuclear deterrence leading to nuclear war, and if that war would be infinitely destructive of human civilisation,  then the world needs to scrap nuclear weapons absolutely and completely.

The possession of nuclear weapons by a number of states in the international community does constitute a system, that is, a group of interrelated parts forming a whole.

Can the system fail? Nuclear deterrence is a complex arrangement of electronic sensors embedded in a command and control network composed of humans working to hard protocols that are interwoven with pattern judgments and valuations which are affected by the emotional state of the individuals and groups that make the judgments. The groups themselves, particularly the supreme decision making groups, are isolated from the common body of humanity, and are known to be susceptible to a condition known as group think – defined as A mode of thinking that people engage in when they are deeply involved in a cohesive in-group, when the members' strivings for unanimity override their motivation to realistically appraise alternative courses of action.[i] Moreover, the interplay of decision makers is now far more complex than in the days of the cold war, with players coming on to the field who might not view the destruction of the prevailing world civilisation as a thing to be avoided at all costs, and other players already on the scene who believe that nuclear weapons could be used tactically without risking a strategic exchange.

In conclusion, it is entirely reasonable to judge that the probability of failure of the nuclear deterrence system is greater than zero. [ii]

Now to the second question: Would the breakdown of nuclear deterrence be infinitely destructive of human civilisation?
This is a point that must be settled by a value judgment.

First, would it be possible to get away with a limited exchange, or would one nuclear detonation inevitably escalate into an all out global nuclear war?

It is impossible to give a definitive answer to that question, but the safest assumption to make is that if one weapon is detonated, they will all be fired. The reason for this lies in the doctrine of first strike, which aims to destroy the opponent’s weapons before they can be fired. Once it is known that an opponent has detonated a nuclear weapon, the pressure will be on for supreme commanders to fire all their nuclear weapons before they lose them to a first strike. In view of this, although we cannot say that any exchange would inevitably lead to a first strike, it would be the height of folly for anyone to assume that they could use weapons in a limited tactical strike and believe that matters would then be allowed to rest by the opposition.

Unfortunately this limited tactical strike idea is the prevailing nuclear doctrine of the United States of America. They consider that nuclear weapons could be used tactically, as an extension of a conventional military campaign. In doing so, they may trigger an all-out nuclear war.

Now, would an all-out strategic nuclear exchange be infinitely destructive? There are estimated to be at least 27,000 nuclear weapons in the world held by at least eight countries, 96 percent of them in the possession of the United States and Russia. [iii]

The effects of all-out nuclear war were well studied in the 1980s. Physically, the most interesting possible effect is the so-called Nuclear Winter, where atmospheric soot cuts off sunlight for a period of weeks or months.[iv] When the sunlight returns, the effects of city and forest fires will have been to increase the atmospheric CO2 load, thus exacerbating global warming. Species loss will increase, secondary to habitat loss. Of these, the loss of bees will be most important, since cessation of their pollination services will lead to failure of such crops as survivors may try to plant. Ironically, rats and cockroaches are resistant to radiation, and so will flourish, given the plentiful quantities of human and animal carrion available.

To say the least, economic growth after a nuclear war would be unlikely. In fact a global economic depression is almost inevitable. The surviving peoples will depend on a survival economy based around obtaining water, food, warmth and shelter for local groups as best they can. Life will be short, and cancers plentiful, but health services would be rudimentary, and analgesics in short supply. Gangsterism, like the rats, will flourish, and self interest is likely to become the ethical norm.

Self esteem, as members of a species that has made such a catastrophic error, will generally be very low. Post traumatic stress disorder and depression are most likely to be the psychological norm.

In summary, it is entirely reasonable to expect that an all out nuclear exchange would lead to the end of western civilisation.

In terms of the model set out at the beginning, the consequences of the failure of a nuclear deterrence system would indeed be infinitely destructive to our civilisation, the probability of its failure is greater than zero, and therefore it is illogical for our civilisation to use that system.

Since the syllogism contains a value judgment, and since there is such commitment to NWMD, as noted above, there will inevitably be those who take a different view. However, they are compelled to argue either that the deterrence system is perfectly safe, which is manifestly not the case, or that a tactical weapon would not lead to an all-out nuclear war, which is clearly not provable, or that an all-out nuclear war would not destroy civilisation, which is clearly unreasonable.

In the circumstances, however, because of the uncertainties involved, it is safer to take a precautionary view. The great majority of humanity view the possibility of all out nuclear war with a great deal of distaste. They should be helped to understand that the nuclear deterrence system is not infallible, and that these weapons are quite capable of being used in anger. This should then motivate them to exercise their democratic right and duty to remove from political office anyone who believes that it is reasonable for any state to possess nuclear weapons.

Once more, Foreign Minister, I thank you most sincerely for your initiative, and I hope that the above will be of some small help to your endeavour.

Sincerely yours


Dr Richard Lawson

[i] Janis, Irving L. Victims of Groupthink. Boston. Houghton Mifflin Company, 1972, page 9.
[ii] Lachlan Forrow and others, "Accidental Nuclear War --A Post Cold War Assessment," NEW ENGLAND JOURNAL OF MEDICINE Vol. 338, No. 18 (April 30, 1998), pgs. 1326-1331
[iii] http://en.wikipedia.org/wiki/Nuclear_weapons (4 June 2007)
[iv] Nuclear winter: Physics and physical mechanisms," R. P. Turco, O. B. Toon, T. P. Ackerman, J. B. Pollack and C. Sagan, Ann. Rev. Earth and Planet. Sci., 19, 383-422 (1991).

Thursday, December 11, 2014

Privatisation - Is it more efficient?

And the animals all began to chant, PRIVATE GOOD, PUBLIC BAAD

We have had a lifetime of privatisation from Thatcher, Blair, and now Osborne.
MPs and journalists in unison bleat the mantra "Private good, Public Baaaad".

It is time to look to see if privatisation actually lives up to its promise of greater efficiency.

So, does it?

No.

The European Public Service Unions looked at 9 sectors where privatisation had taken place, and  found no evidence that private is more efficient.

The excellent New Economics Foundation, nef, looked at privatisation of rail, health and prisons. here are some highlights.

Rail
Railways lost traditional bonds and transmission of skills and experience. The complexity introduced meant that literally hundreds were employed solely to apportion blame for trains being late.

State support for rail had to increase after privatisation


Healthcare

Life expectancy rises with health expenditure, but the USA with its 100% private health, does very badly.


The Tories deny that their reforms are an act of privatisation, but since the Lansley Act, 1/3 of new contracts have gone to private providers.

Prisons

Ohio found that re-offending was higher in private prisons
Private prisons are more expensive.

Conclusion

The UK, and indeed the whole world, is being taken for a ride. By private providers of course.

Not convinced? Try this more in-depth account.


Sunday, December 07, 2014

Testing Re-Purposed Medicines In the 2014 Ebola Outbreak



Abstract

This paper relates specifically to the pharmaceutical response to the outbreak of Ebola Virus Disease (EVD) in West Africa. It advocates the use of drugs (some listed in the Appendix) that already have an established place in other fields of medicine, and that have been shown in animal studies to be effective in reducing the life-threatening “cytokine storm” associated with some infections, but that have not been through the normal process of human trials in EVD. These medications should be re-purposed for use in EVD, and their efficacy tested in simple field trials.
Education (“sensitisation”) about the way that EVD is transmitted is absolutely vital in prevention of spread, and re-hydration and correction of metabolic abnormalities rightly remain the mainstay of therapy in EVD. We must make sure that enough materials, skills and personnel are available to maintain these general supportive measures, but at the same time, we must look for medicines that can increase the recovery rate.

Treatment approaches

Rapid development of vaccines is a hopeful avenue of progress[i], but the limitation with vaccines is the lag between gathering evidence that they are effective, and producing sufficient doses to meet the need of the whole population. However, they certainly will have a role in protecting the very courageous medical and nursing staff.
“Convalescent Serum” - transfusions of serum from patients who have recovered from the infection is being tested[ii]. This approach has the clear advantage that the supply is provided by grateful recovered patients, and will therefore be more commensurate with the demand. It is promising, and is under development[iii], although preparation of safe, pure serum will be challenging and costly. If we can increase the recovery rate, more serum will become available.
Established anti-viral agents such as Brincidofovir are also being tested.
The World Health Organisation confirmed on 12th August in Geneva that the use of untested drugs on Ebola patients would be ethical[iv]. “On 11 August 2014, WHO convened an Ethics Panel to consider and assess the ethical implications of the potential use of unregistered interventions. The panel reached consensus that in the particular circumstances of this outbreak, and provided certain conditions are met, it is ethical to offer unproven interventions for which the safety and efficacy have not yet been demonstrated in humans as potential treatment or prevention… In addition, existing drugs approved for other conditions, which show good evidence of activity against Ebola in laboratory models, may be evaluated and ‘re-purposed’ for use, if efficacy is demonstrated.[v] Note that the only way of demonstrating efficacy is by trials in the field. However, the meeting decided to concentrate efforts on a small number of potential treatments, notably convalescent serum and vaccines, and there was no resolution to further explore the use of re-purposed drugs.
Meeting in Geneva on 4-5th September 2013[vi], WHO participants concluded “the highest therapeutic priority should be given to human convalescent serum, whole blood, and blood products. It was proposed that survivors of EVD should be followed up carefully, not only to determine the long-term effects of EVD, but also to identify potential donors of blood for therapeutic use. The next priority would be the promising vaccine candidates and potential therapeutics”. Perhaps regrettably, the use of re-purposed medicines was not prioritised at this meeting.
The reason given for this decision is that the challenges of field testing of any medical intervention are daunting. “For any study to be planned and then conducted, there is a need for a number of key players to be fully behind and aligned: manufacturers/developers, regulators both in the affected countries and other regions, WHO, MSF and other NGOs who are providing help locally[vii].
This decision suggests that organisational difficulties are inadvertently inhibiting chances of improvement in the medical treatment of a serious epidemic. Such difficulties can be overcome, given political will. If manufacturers, national health services and NGOs can agree, trials of re-purposed medicines, could go ahead. We should therefore consider how this roll-out could be designed.

Trials of re-purposed medicines

In a situation where patients are dying because there are not enough nurses to attend to them, a full research effort which stands a chance of being published in a peer-reviewed journal would be inappropriate and incongruous, since, unlike practical medicine and nursing in a developing world setting, research requires a full complement of staff and very high standards of control of the patient’s situation. However, the demands of perfection must not be allowed to stand in the way of medical progress.
To insist on classically perfect study conditions is to insist that very little research will be carried out during the present epidemic – or indeed, any epidemic of this magnitude. This would be irrational. It is highly likely that in coming years, medicine will encounter an epidemic with a comparable mortality rate to EBV, but with air-borne transmission, which would make it a far greater challenge. In this event, we will need all the help we can get, and it would be deeply regrettable if medicine is lacking inexpensive and effective ways of treating a disastrous epidemic simply because it is deemed that re-purposed medicines are not worth testing in the present outbreak. The West African Ebola epidemic presents us with an opportunity to learn about controlling the cytokine storm. We may find that it is impossible to do so with re-purposed drugs. Equally, we may discover that they are helpful additions to existing supportive treatments. 

Study design

The present proposal is that we should carry out a number of very simple tests for re-purposed drugs as follows:
1.        A research team approaches a field treatment centre and explains that if the staff wish to collaborate, they will be supplied with medications, some of which will be Preparation A and some Preparation B. One of them is a dummy, one is a drug that is used in other fields of medicine, that has demonstrated efficacy against fever in animals, but has not yet been tried out on humans. It is explained that there is no guarantee that the preparations will work to help patients with EBV, but that there is a chance that a new therapy for Ebola may be discovered by their work.
2.        If the treatment centre staff agree, a trial is commenced. The initial dose given will be a fraction of the smallest dose used for the medicine’s official indication, the dose to be decided by consideration of the drug’s known side effects.
3.        One or two research workers will join the treatment centre team to supervise delivery of medications, and to collect the data.
4.        The endpoint will be death or discharge from hospital. If possible, changes to the patient’s condition and possible side effects will be noted.
5.        If a statistically significant advantage emerges from the data, the code may be broken, and if improvement is associated with the active drug, the trial will be repeated at a higher dose.
6.        If there is no difference between the placebo and the active drug, the trial will again be repeated at a higher dose.

If any significant differences emerge between outcomes for placebo and trial drug in these pilots, more elaborate and extensive trials will be run.
Results from the various treatment centres will be collated and reviewed.

Appendix: Medications that can be re-purposed to treat EVD

Cytokine storm is an exaggerated reaction on the part of the cellular immune system. A positive feedback loop forms between cytokines released at the site of infection, which attract more defence cells, which produce more cytokines. It is this vicious circle that causes Ebola infection to have such high mortality. 
OX40 is a protein secreted by T-cells that keeps them from dying, and therefore perpetuates the feedback loop. OX40 IG is a synthetic immunoglobulin that neutralises this protein. It has been shown to be effective in mice[viii]. It was tested in 2003, but it seems that it was bought by a venture capital group that decided not to develop it.
Some of the drugs mentioned below act on cytokine storm, but others have other modes of action.
The following are some examples of drugs that can be re-purposed:
1.        Simvastatin and Gemfibrozil, both lipid-lowering drugs in common use, have been shown to have an effect in reducing the cytokine response. In the case of Simvastatin, an effect has been shown in humans, albeit not in acute infection. Simvastatin also has an effect on the replication of some viruses. It decreases OX40[ix].
Terblanche has produced an excellent review of the immunomodulatory and antiviral effects of statins[x].
2.        ACE Inhibitors and Angiotensin II receptor blockers are medications in common use against hypertension. The Renin-Angiotensin System (RAS) is involved in the cytokine storm[xi]. ACE is involved in pulmonary inflammation[xii],[xiii]. They have been shown to reduce the cytokine feedback loop[xiv]. Examples of ACE inhibitors are ramipril, perindopril and Lysinopril. Angiotensin II blockers: losartan, candesartan, valsartan. Care must be exercised in using these in Ebola, as their hypotensive effect may aggravate any hypotension present due to dehydration.
3.        TNF Blockers are medications routinely used in arthritis and other inflammatory conditions, and work by inhibiting Tumour Necrosis Factor (TNF) which is implicated in cytokine storm. Some are monoclonal antibodies (infliximab, adalimumab, certolizumab), and some are more simple compounds such as bupropion, in common use in smoking cessation.
4.        Naltrexone, a long established opioid receptor antagonist, may inhibit cytokine storm. There is evidence from animal studies[xv],[xvi],[xvii],[xviii] that shows it may be clinically effective. It is inexpensive.
5.        Selective estrogen receptor modulators (SERMs) such as clomiphene, commonly used in treatment of infertility and breast cancer, have been shown to inhibit the Zaire strain of Ebola Virus in vitro and in vivo, in mouse studies[xix].
6.        Ion channel blockers such as Amiodarone commonly used in treating hypertension, have been shown to have an effect on the entry of filoviruses into cells[xx].

Note that these medicines are already in use, and therefore have been tested for human acceptability, although not specifically in patients with fever. Their side effects and contra-indications are known. They are relatively inexpensive, and can easily be made available in quantities sufficient for initial trials.
It is self-evidently true that we do not know what happens when these drugs are used in patients infected with the Ebola virus, but the only way to find out in good time is to test them in the field. They may have adverse effects in the given situation, they may have no benefit whatsoever, but equally, one or more of them, alone or in combination, may prove helpful, and the exercise will then have been at least worthwhile, and even, possibly, game-changing.
In conclusion, there are several modalities of treatment for Ebola that must be tried in the present outbreak. Their deployment will be “off-licence” and their efficacy must be monitored, but to subject them to trial in the Ebola situation that we are currently engaged with is ethical and perfectly rational. It is hoped that the small initial pilot studies outlined in this paper will be rolled out as soon as possible.


Dr Richard Lawson MB BS, MRCPsych
Churchill,
North Somerset, UK
Sunday, 07 December 2014





[vii] Enrica Alteri MD, Head of Human Medicines Evaluation Division, European Medicines Agency, personal communication

[viii] Humphreys I R, Walzl G, Edwards L, Rae A, Hill S, Hussell T. A Critical Role for OX40 in T Cell-mediated Immunopathology during Lung Viral Infection. The Journal of Experimental Medicine 2003;198:1237-1242
[ix] Liu B, Yu G, Yang Z, Sun L, Song R, Liu F, et al. Simvastatin Reduces OX40 and OX40 Ligand Expression in Human Peripheral Blood Mononuclear Cells and in Patients with Atherosclerotic Cerebral Infarction. The Journal of International Medical Research. 2009;37:601-10.
[xi] Genctoy, G; B Altun et al. (February 2005). "TNF alpha-308 genotype and renin-angiotensin system in hemodialysis patients: an effect on inflammatory cytokine levels?". Artif Organs 29 (2): 174–178.
[xii] Marshall, RP; P Gohlke et al. (January 2004). "Angiotensin II and the fibroproliferative response to acute lung injury". Am J Physiol Lung Cell Mol Physiol (Royal Free and University College London Medical School) 286 (1): 156–164. PMID 12754187.
[xiii] Moldobaeva, A; EM Wagner (December 2003). "Angiotensin-converting enzyme activity in ovine bronchial vasculature". J Appl Physiol (Department of Medicine, Johns Hopkins University) 95 (6): 2278–2284.
[xiv] Ruiz-Ortega M, Ruperez M, Lorenzo O, Esteban V, Blanco J, Mezzano S, et al. Angiotensin II regulates the synthesis of proinflammatory cytokines and chemokines in the kidney. Kidney Int. 2002;62(S82):S12-S22.
[xv] Peng X, Mosser DM, Adler M, et al. Morphine enhances interleukin-12 and the production of other pro-inflammatory cytokines in mouse peritoneal macrophages, Journal of Leukocyte Biology. 2000;68:723-728.
[xvi] Hola N V, Zaji Cova A, Krulova M, Blahoutova V, Wilczek H. Augmented production of proinflammatory cytokines and accelerated allotransplantation reactions in heroin-treated mice. Clinical & Experimental Immunology 2003;132:40-45.
[xvii] Lin S L, Lee Y M, Chang H Y, Cheng Y W and Yen M H. Effects of naltrexone on lipopolysaccharide-induced sepsis in rats. J Biomed Sci. 2005;12:431-40. 
[xviii] Greeneltch KM, Haudenschild CC, Keegan AD, Shi Y. The opioid antagonist naltrexone blocks acute endotoxic shock by inhibiting tumor necrosis factor-alpha production. Brain Behav Immun. 2004;18:476-84.
[xix] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3955358/
[xx] http://jac.oxfordjournals.org/content/69/8/2123

Saturday, December 06, 2014

Osborne's shattered economic plan put in context


Above is George Osborne's economic plan. On the left, in brown colour, is the projection he made in 2010, with the deficit - the difference between Government expenditure and income - falling year by year until it is gone in 2016-17. In red, we see what actually happened, with the deficit way above his projection. In pink, we have his present projection, from last Thursday. Again, as in 2010, he projects a falling away to nothing in the next 5 years.

Are we to believe him? Only the Tory press and their dupes believe him.

The UK economy is rarely not in deficit. Here is the trend since 1980:

Note that the yellow bit on the right is Osborne's 2010 projection, the brown in the top figure. Note the rarity that it crosses the line into surplus. Note that Labour under Gordon Brown inherited a surplus and held the deficit down until 2008, when he got generous with education and the NHS, and then the spike in 2009, when the idiot/criminal banksters blew the whole thing apart. 

Let's look further back, to 1948. Here we can see a definite trend towards greater deficit. 


Osborne was able to browbeat the UK voters on the necessity of austerity on the basis of big deficit figures, but only because the media, in the main, colluded with him, either out of stupidity or because they share his ideological belief that all state spending is bad.

One factor in the increase in the deficit is that most money is created out of debt. The more money is in circulation, the more debt in existence.  Here is a post on why debt is breaking the world economy.

The real answer to deficit is not to shrink the state, which is what Osborne wants to do,  despite the horrendous effect it will have on the UK, but to take back the monopoly of creating money from the banks.

Voters are not stupid. They dismiss Osborne's plan by a margin of 2:1
source: http://t.co/eWsI7kzb3m


This is all a good reason to vote Green in  May 2015, since the Green Party is the only party that wants to do this.

Meanwhile, we have to grit our teeth while the papers and the BBC parrot Osborne's lies.