Thursday, May 20, 2021

Review: Sex at Dusk by Lynn Saxon

I read this book a second time recently.  

I appreciate that such a scholarly and well-researched text was written by an amateur scientist.  It was written as a critique of a more popular book with a similar title.  This other book attempted to make a case that humans in the pre-agricultural era (i.e. over 10 000 years ago) had a much more promiscuous lifestyle, which for them was supposedly healthier and more peaceful--then with the implication that we should try to emulate this in modern society.  

Saxon's book looks at almost every claim made by the other authors, and shows how their analysis was biased, incomplete, or just completely wrong, in terms of historical and anthropological data, as well as genetics and evolutionary biology.  Saxon shows that the authors of the other book particularly do not address the very dark side of almost every case study described.  The areas of focus in both books include social and sexual behaviour in primate species most closely related to humans (chimpanzees, bonobos, and gorillas), as well as cultures of remote present-day groups, such as those living in the Amazon.   A particular emphasis is the genetic basis (through natural selection) of behavioural traits.  

The subject of the genetic foundations of animal behaviour, and of the mechanism of evolution through natural selection, should be part of everyone's common knowledge.  Books by naturalists, biologists, or geneticists on this subject are not only informative from a scientific point of view, but are fascinating in the same way that watching a good nature documentary would be:  most of us are unaware of the life cycles and behavioural patterns of most of the species with whom we share the earth.  The stories, often about species that many of us have never heard of, but also sometimes about familiar species, are almost always interesting, but sometimes shocking or disturbing or intensely dramatic.  The best science writer in this genre is Richard Dawkins -- whether or not you like his philosophical point of view, it is essential and often entertaining reading to learn about other species, with the eye of a great naturalist.  

Saxon shows that we cannot escape some of the problems which exist in relationship and sexual dynamics in humans, including jealousy.  There is a strong genetic foundation for pair bonding in our species, though not without tensions, jealousies, and strong desires, which differ between the sexes, to have other relationships outside of the pair bond; but such excursions outside of a pair bond cannot occur without a substantial cost, often manifest in behaviour which is in part genetically determined.  

None of these genetic factors justifies a social policy which constrains relationship choices... social and relationship freedoms, as well as guaranteed personal rights, are aspects of social justice that have thankfully grown in our country in the past century; they must be created and legislated, whether or not they have always been favoured in our species through genetic/natural selective forces in the distant past.  

Thursday, May 6, 2021

Review: Capital in the Twenty-First Century, by Thomas Piketty

 Thomas Piketty is a French economist, whose book "Capital in the Twenty-First Century" is a great analysis of the history of wealth, economic inequality, and taxation through the past two centuries, focusing especially on Europe and North America.  

I highly recommend this book.  It is very long and detailed, and much of it is hard to understand fully for a person not experienced in economics or finance.    For a brief introduction to Piketty's work, there is a good documentary with the same title, which is also worth watching.  But the documentary does not contain nearly as much detailed analysis of the problems and proposed solutions, compared to the book.  

This book is important to read, to become familiar with these issues.  We all pay taxes, and most of us complain about them, but few of us understand the history of taxation, and the reasons why taxes are the way they are.  Even for those who are experts in the area, it seems to me that relatively few people (such as economists) have a good understanding of economic history.  

Piketty shows that income inequality was extremely high in the 1800s in Europe, leading to some people with enormous estates, while much of the population lived near or below the poverty line.  Most of the wealth in the society was owned by a very small number of people.   This changed dramatically mainly as a result of the world wars, and the resulting policy changes after the wars.  

Prior to the wars, those with enormous wealth paid very little tax, and this wealth was also passed through inheritance with very little tax either.   After the wars, progressive taxation of income and estates led to a large improvement in this type of extreme inequality, and allowed a much larger number of people (such as those in the middle class) to own a larger portion of national wealth.   

Interestingly, the United States in the 1950s-1970s had one of the most fair and progressive taxation schemes in the world, leading to improvements in economic inequality, before regressing substantially in the 1980s and beyond.  

Piketty shows that there are not only political and social consequences of having a society allowing extreme wealth to accumulate for a small number of people, without those people having to earn this wealth through work, there is also an economic consequence, since economic efficiency is not well-served or incentivized this way.   

His suggested solutions to this problem include having a progressive income tax, a progressive tax on estates & inheritance, and a progressive tax on capital or total personal wealth.  By progressive, he means paying a higher rate for higher levels of income, and a lower rate for lower levels.  At present, there are many examples Picketty shows where the system is not progressive, but regressive--that is, people with extreme levels of wealth actually pay an overall lower marginal rate on their vast incomes, compared to those in the middle class.  

The main barrier to a progressive tax on capital (i.e. a tax on invested fortunes), is that such investments are often hidden; many extremely wealthy people hide their wealth in offshore banks, etc. so it is hard for governments to understand how much wealth there is.  These are so-called "tax shelters."  In order to solve this problem, governments across the world would have to come together and cooperate with sharing banking information, to create a type of global wealth census, or "cadastre."  

How is this relevant to psychiatry?  Economic issues, including poverty, are extremely important in the causation and management of mental health problems.  Universal health care, and universal comprehensive education (including university  college, or other training) is possible in all countries, and can be improved where it currently exists, such as in Canada.  But health care is expensive, and needs to be fairly subsidized.  Taxation issues obstruct the provision of efficient social services, including health care.  

Also, greed in general, without a principle of making social or community contribution, is a factor contributing to declining mental health, and to more social problems including crime.  

I did not find Piketty's analysis or recommendations to be "radical" at all.  They are not in opposition to free-market economics, but rather are supportive of a system where markets could be free for all, without rapidly escalating and uncontrolled excesses.  

Monday, January 11, 2021

COVID-19, Psychiatry, and Politics: an update and reflection on 2020

 COVID-19 update January 2021

I come to this issue as a psychiatrist.  I am not an infectious disease specialist, immunologist, virologist, or epidemiologist.  But I am well-educated in all of these fields, at least to an undergraduate and MD level,  boosted further by my background in mathematics & statistics.  As an undergraduate science student another of my special interests was microbiology. I have always tried to follow developments in general medicine and medical research over the years, alongside developments in psychiatry.  Epidemiology and the science of efficient, valid study design and data analysis are essential components of modern psychiatry.  

I also have personal experience with this issue.  A close family member nearly died of COVID-19 and most likely will have long-term serious health consequences despite having survived.  One family member works on an acute COVID ward.  Four other family members are physicians or nurses working in acute care medicine and are in close proximity to this issue in their practices.  Another close family member is a virologist, part of a Canadian team that studies COVID-19 and is developing another vaccine.  An increasing number of colleagues, friends, and patients have been affected by the virus.  

This bears no similarity whatsoever to any other infectious disease epidemic that I have seen in my lifetime.  It is nothing like the seasonal flu. 

COVID-19 is the worst public health catastrophe to have befallen the world since the great pandemic of 1918.  

There have been about 2 million deaths due to COVID-19 in the world so far.  This is a tiny fraction of the number of deaths that would have occurred if we had carried on as usual, as though this were an ordinary outbreak of the flu.  

Let’s imagine that we had not introduced any significant public health measures, and that we had treated COVID-19 like any other seasonal flu outbreak: 

The current understanding of COVID-19 mortality risk, of about 1% overall, would imply a total anticipated worldwide death count of 50 million if no public health measures had been taken to slow the spread of the disease, mostly over the course of one year.     That represents over 500 million years of life lost, equivalent to all the years of life lost from murders and other violence in about 20 years of time.  

But these 50 million deaths do not even begin to estimate the other impacts on the population that would have happened: 

Hospital wards and intensive care units would have been overflowing for a year or more, leading to many more deaths: people with other diseases and injuries would have been unable to access care, forcing healthcare professionals to let many people die without the curative treatments that otherwise would have been available.  Unfortunately we see this going on right now in many places of the world, including in Canada, despite the strong public health measures we have taken.   

Dealing with such devastating trauma would have caused many healthcare workers post-traumatic illness, in many cases for the rest of their lives.  Many workers would have had to leave their careers.  Many would have died by suicide.    For such workers, it would be equivalent to working on the front lines of a major war on a daily basis for an entire year.  Unfortunately, this is going on in many areas of the world, despite the measures taken.  

And, unlike other epidemics of viral respiratory disease, COVID-19 has a clear propensity to cause lasting tissue damage, not only to the lungs, but to other organs including the brain.  There would have been a much higher burden of  lasting or permanent disability as a result, if the disease had been allowed to spread unchecked through the population.  

For people who have shockingly had doubts about the severity of the situation, I have wished that they could visit the many patients in agonizing, suffocating respiratory failure on their journey to a nightmarish ICU stay.  Ironically, the good public health measures in many places have limited ICU overflow, so that relatively few people in these places know any friends or neighbours who have suffered this way—but because of this success, many poorly-informed people do not have a realistic understanding of the horror of the situation. 

The strict measures we have taken have absolutely been necessary to prevent the present catastrophe from being a hundred times worse.  

But the measures were not nearly enough, except in a few countries.  

It is fair enough to observe that if a vaccine, massive-scale testing,  or effective acute treatments had been impossible to achieve, it would have made sense to just let the disease gradually run its course, with just enough public health intervention to prevent the hospitals from overflowing.  

But most of us were optimistic enough to anticipate that a vaccine and other treatments would be developed over the space of months to years, therefore it was imperative to slow the spread as much as possible, not only to delay deaths and suffering, but to prevent them entirely and allow a return to full normality.  

Here are some thoughts of other measures that I think would have been necessary or helpful:  

1) One of the unique aspects of COVID-19 is its very strong age-dependent morbidity and mortality characteristics.  In young, healthy adults under 30, it is indeed usually (though not always) a mild or even trivial viral infection.  But with every advancing year of the victim's age, the disease becomes more deadly.  

This fact, in my opinion, could have been used to design some very simple basic research studies.  It would involve healthy young volunteers, fully informed of risk, to be exposed voluntarily to the virus in a quarantined, medically-supported setting.  The risk would be comparable to that of volunteers for military service. 

This would have allowed research to determine the exact effect size of measures such as mask usage, mask type, ventilation effects, and inoculum size, in determining rate of spread and severity of ensuing disease.  We would know exactly the likelihood of airborne spread, fomite spread, and direct contact spread, therefore guiding us about optimal preventive measures.  

Right now we have very good evidence about the usefulness of masks to reduce viral spread, but a prospective, controlled study in humans would show, beyond the shadow of a doubt, with the highest standards of scientific reliability, the exact effectiveness of widespread or solitary mask use.  When equipped with the unequivocal study data, governments could then have invested appropriately in mask manufacturing for the whole population (including high-grade N95 masks if needed).  

I suspect the results would have shown a significant but modest benefit of masks, with better effectiveness for higher-grade medical masks.  This could have generated a massive government intervention to supply such masks and mandate them for the whole population, using war powers of the government to compel industrial production.  

Such studies would also have shown, with absolute proof, the degree and length of immunity conferred by prior COVID infection, and also whether disease severity would be impacted by inoculum size.  If a smaller inoculum led to milder disease, this would be another reason to mandate mask use.    

Such studies would also have been ideal to quickly test treatment strategies.  The whole hydroxychloroquine fiasco, which the world saw earlier this year, could have been dealt with and resolved within a month or so, allowing us to move on more quickly to find other treatments that could have been more effective.  As it was, hydroxychloroquine became yet another issue tainted by propaganda, misinformation, and mind-numbing ignorance about how to conduct valid medical research.  

Such studies could have demonstrated the degree to which major ventilation improvements in indoor settings (such as with MERV-13 or HEPA filtration at a high number of air changes per hour) could have reduced the risk of viral spread, particularly when combined with modest distancing measures.   This would have allowed us to determine effective safety protocols for settings such as classrooms and restaurants, possibly allowing all of these establishments to operate more safely during the pandemic.  Alternatively, the data might have shown that safety would not improve much with these measures, requiring that such settings be at least temporarily shut down.  

The studies would also have had the benefit of most likely producing an increased number of immune individuals, thereby preventing participants in the study from ever spreading the virus to anyone else. 

A modification of this study approach, which should still be done, and is uncontroversial, is to do more substantial animal studies to demonstrate airborne spread characteristics and the effect size of ventilation improvements.  

2) Ventilation

Thankfully, mask mandates have become much more a norm, though this should have been done many months sooner.  

A relatively neglected issue, which could be simply addressed, concerns improvements to interior ventilation, given evidence that COVID is spread at least in part through airborne transmission.  If every classroom, workplace, restaurant, and home, had simple ventilation improvements (open windows, HEPA filtration, etc.) there could be a significant reduction in the risk and rate of spread. 

Each individual method (distancing, limitation of the size of groups and time spent in group spaces indoors, masks, ventilation, disinfection) has a limited effect size, but in combination, if done consistently, lead to much more substantial protection.   

3) Mass testing

The development of population scale rapid, frequent virologic testing could also have led to a rapid end to the pandemic, while allowing much more freedom to work & socialize.  If every person in the population was tested daily or weekly, every positive person could have isolated for a few weeks; this would rapidly have limited cases.  This approach alone could theoretically lead to the extinction of the virus.  I do not know what type of technological limitations impeded this approach, but it seems to me an area that was never developed as fully as it could have been.  I suspect the vast resources of the US science, technology, and manufacturing community could have led to big developments in this area, if the government response had been more normal.  

2) Media and Political Issues

I am ashamed to observe that most of the medical community, and in particular the psychiatric community, has not had the courage to comment on political factors which have led to immense, needless, catastrophic suffering for individuals, economies, and the world as a whole.  

Prior to 2021, Canada's southerly neighbour was afflicted by a devastating failure of leadership.  We are afraid to comment, as professionals, about psychopathic and narcissistic traits accompanied by staggering incompetence, ignorance, self-absorption, affective instability, almost continuous lying, and callous disregard, in a major political leader.  It does not require advanced therapeutic insight to see this--the behaviours were in plain view on almost a daily basis for years.   I am reminded of a cartoon or fantasy villain, with a team of minions, not unlike the villain from a "Batman" movie or a Tolkien novel, with just as much power, though with less intelligence or criminal aptitude.   I am also reminded of a caricaturized bully character from film, such as "Biff" from "Back to the Future."  

If similar behaviour had been going on in the partner of one our patients, I am quite certain we would come out and at least speculate directly about this with our patient, with a message of stern warning In this case, the "patient" is an entire nation, and the "partner" is an extremely unstable, abusive leader, but one whose demagoguery and propaganda have allowed a significant segment of the population to remain devoted, as though members of a death cult, sometimes to a fanatical degree. 

There has been a devastating barrage of misinformation and propaganda that has caused a bizarre politicization of simple community health measures.  In part, I attribute this directly to the leader, whose egregious incompetence and callous disregard has allowed what could have been an inspired, ingenious response from one of the world's great countries to devolve into utter chaos, madness, and mass death.  This behaviour has affected not only the US but the whole world.  The world's response to COVID has been set back greatly, because the world's leader in advanced medicine and scientific research has been suppressed, languishing in a cloud of needless chaos.  

The US could have engineered a rapid, massive research response, akin to the Manhattan Project, or the race to land astronauts on the moon,  combined with public health measures, to have emerged an inspired leader in this crisis, leading to decades of respect and appreciation from people all over the world, bolstering its image and authority forever.  Many of the world's greatest virologists and other health experts are American, and I can only imagine what sorrow, anger, and frustration they must have had this past year to see their country's disastrous and frightening response.  Not only has the response been catastrophic, the leadership is so steeped in denial about the gravity of the situation, and probably so ashamed of its incompetence, that it is trying to convince people that it was never a serious problem in the first place, that it was all over-blown.  It is like trying to convince people that World War II never happened (interestingly, the total number of deaths in World War II is comparable to the number of deaths that would be caused by COVID-19 if nothing was done about it).  

There are complex causes for this phenomenon, but one element of the problem is the polarization of news information found online.  It is very problematic when a group of individuals holding extreme or delusional views can all meet together on an internet-based forum or social media, and be exposed only to repetition and escalation of their beliefs.  In this way, it is again very much like the dynamics found in cults.  

What can be done about this?  It is a hard problem, but I hope that companies responsible for such polarization, such as Twitter or Facebook, can take much stronger steps to prevent their sites from magnifying extremism and polarization, while still honouring freedom of expression. 

Experts and leaders need to ensure that the entire population has access to good-quality information, and is not trapped in a "news bubble."  

Leadership change is of course a key requirement for problems of this type to improve.

Twitter and other news sites have had a negative effect on my own morale.  I have found that stopping news and Twitter exposure entirely for several months has been helpful.  I think that it would be sound mental health advice for all of us to severely limit the amount of time we spend watching news or engaging with social media.  Probably one hour per week would be a reasonable maximum.  Exposure to standard news sources, such as major world newspapers, should accompany any exposure to "news bubbles."   

In Conclusion: 

I was always an optimist about this problem.  I thought we should have had much, much stricter measures earlier on, so that we could have followed a course similar to New Zealand.  We still should do this, but it is like a forest fire: it is so, so much harder to control it if you have left it burning for a long time, instead of dealing with it properly at the beginning.  I  anticipated that we would develop better treatments or a vaccine sooner than expected, and I am relieved and delighted that this has come to be.  

But the pandemic is not over yet.  We should be fighting hard, with every possible public health measure, until the population is vaccinated.  Then the war will be won, and we can carry on with a more normal life again.  Despite the devastation, we will have learned a lot, and some of our adaptations and innovations will stay with us forever—for example, I predict many of us will continue to do much more remote or video-based work, often from home.  I hope it can be a time of healing, peace, and reconciliation, with preparations and changes put into place to prevent this type of disaster from ever happening again.  

The Next Crisis: 

The next crisis, or at least one of the big next crises, is an even bigger one, which is inexorably coming (it has been happening already for decades): it is environmental degradation and climate change. Unfortunately some of the same factors which caused catastrophic delays in responding to the COVID pandemic are now causing delays responding appropriately to the environmental crises.  We need to be acting now to do much, much more about this.  A starting point for education on this issue would be David Attenborough's documentary, "A Life on our Planet."  It is both a sorrowful, tearful account of the state of the world's environment, but also contains a message of hope and a call for action. 

There is always hope despite the severity of any problem.  It is important not to allow frustration, cynicism,  or despair to deter us from taking the actions we can to help.   

Saturday, July 18, 2020

BC COVID-19 Update, July 18, 2020

The management of the pandemic in BC has been very successful, thanks to everyone's hard work and sacrifice over the past months.

Some of us, such as emergency room or ICU staff, ambulance workers, and staff at grocery stores, have had to take on much more risk than the rest.  We need to show gratitude for this hard work:  the 7:00 PM celebration every day is a small symbol of this.

However, since the restrictions have loosened, we have predictably had an increase in cases again over the past few weeks.

I think there is a significant risk that the cases could escalate again quickly.  Then we would be in the same predicament as in March and April, although I think we would be better prepared.

Here is what we can do right now to prevent cases from continuing to surge, and to maintain our hard-won gains against the pandemic:  

1) People need to wear masks whenever they are indoors around strangers.   This includes in grocery stores, shopping malls, and on public transit.   All staff in grocery stores should be wearing masks.

Masks do not eliminate the risk of contagion, but they very clearly reduce it enough to make a big difference.  Mask use has not been emphasized strongly enough by public health authorities.

I think that we should give free high-quality masks to everyone in the population.  These should be made available at the entrance to every business, and at transit stations.  A home-made mask is fine--anything is better than nothing.  A good medical-quality mask is better, and an N95 is best of all.  Masks are available for sale at retail outlets such as Canadian Tire.

The evidence that has accumulated over the past months has shown a much lower risk of contagion outside, including in groups.  So I am much less worried about the need for a mask mandate outdoors, although I continue to think that the more mask use the better, when around other people.  I do think that there should be a mask mandate for grocery stores, shopping malls, public transit, and other indoor spaces in which strangers could meet each other.  

2) Maintain social distancing, also known as "physical distancing."  The farther you are from an infected person, the smaller the risk of contagion.  During the whole pandemic we have recommended 2 metres, or 6 feet, of distance between people.  I recommend this as a bare minimum.  The more distance, the better.  Social distancing is absolutely crucial if you are in an indoor environment.

3) Grocery stores and other businesses should continue to limit the number of people allowed inside at one time.

4) I think that if you are going to a restaurant, you should take out.  Sitting inside at a restaurant is a needless high risk activity.  The thought of opening bars seems like madness to me.

The evidence in the past months has also showed that the main route of contagion is through respiratory droplets.  There may be a small degree of true "airborne" transmission, but most spread is through close contact indoors with an infected person.  Many such infected persons do not have any symptoms, so there would be no way to know you are in contact with someone who has the infection.

The risk of such spread is greatly increased when people are talking, shouting, or singing, and the probability of contagion of course increases with the duration of time spent in a high-risk environment.     So a restaurant meal indoors around strangers, all of whom talking and laughing without masks, is very high risk.  The ventilation system in such an enclosed space can cause contagion in people downstream with respect to the air flow.

5) We are enjoying more social contact with friends and relatives, but we should continue to maintain a limited social "bubble."  Now is not a time to be inviting new friends to your home, or having dinner parties.  If you want a social dinner, consider having a picnic or a barbecue outside.

6) Hand-washing practices and cleaning surfaces such as doorknobs or shopping carts, are still recommended, but my reading of existing evidence is that contagion from surfaces (so-called "fomite transmission") is not likely.  The main mechanism of spread is through respiratory droplets in the air, spread by coughing, sneezing, talking, or simply exhaling.  Therefore, we should maintain good hand-washing practices but we do not need to be as worried about this, and we do not need to frantically increase efforts to sanitize surfaces.  Our efforts should be spent primarily on reducing contact with strangers, reducing contact with crowded indoor spaces, increasing mask use, and maintaining social distancing.

7) Working from home should be encouraged whenever possible.  An office workplace, with people in close proximity without masks, is very high-risk in my opinion.  Government support should continue to allow working from home, and financial support for people who need to take a leave from work.

8) I do not support any plan of students returning to attend classes indoors.  If there could be group activities planned for outdoor learning, in conjunction with video lessons from home, this might be a reasonably safe balance.

9) On a community level, the more we can increase testing and tracing, the better we will be able to control, or even end, the pandemic.   We can learn from other places that are controlling the pandemic very well, such as South Korea and Germany.   For example, if a home-test kit was available, manufactured with massive government-supported investment, freely provided, and if every person in the population could test themselves weekly, we could rapidly isolate almost every COVID-19 carrier, and the pandemic would be over within a month or two.  Such mass-scale testing is far from being available, but this thought experiment demonstrates how incredibly important it is to test as much as possible, including random people in the population, and people without symptoms; from there it is essential to have a system to isolate every person with a positive test as quickly as possible, as well to inform and temporarily isolate any known contacts.  This system takes leadership, organization, a vast investment of money, commitment, and hard work to set up and run. 

10) Follow reliable sources for information.  In BC, we are fortunate to have Dr. Bonnie Henry, who has been a great leader through this emergency.   There are good people to follow on Twitter for COVID-related information:  for BC news, there is @BCGovNews.  I recommend Eric Topol (@EricTopol), Max Roser (@MaxCRoser), Nicholas Christakis (@NAChristakis), the Canadian ID physician Isaac Bogoch (@BogochIsaac), David Boulware (@boulware_dr), @AndyBiotech, and for some more sophisticated virology, Professor Akiko Iwasaki (@VirusesImmunity).  There are many others, but I think these are a good start.

Tuesday, May 26, 2020

15 Average Years of Life Lost for each COVID-19 death

The following is a very rough estimate, which would be subject to refinement or correction, but I believe it is reasonably accurate.  

Here are some calculations to show approximate average years of life lost for each COVID-19 death in the population.  They are based on mortality statistics of COVID-19 deaths, 
which shows that about 49% of people dying were age 75+ (each of whom lost 6 years of life on average); 25% of people dying were ages 65-75 (each of whom lost about 15 years of life on average); 22% of people dying were ages 45-64 (each of whom lost about 30 years of life on average), 4% of people dying were ages 18-44 (each of whom lost about 55 years of life on average), and 0.05% of people dying were younger than 18 (each of whom lost about 70 years of life on average).  

Therefore the average years of life lost for each COVID-19 death is 
(0.49 * 6) + (0.25 * 15) + (0.22 * 30) + (0.04 * 55) + (.0005 * 70) = 15.525

So each COVID-19 death in the population leads to an average loss of 15 years of life.

The calculation is based on tables of COVID-19 deaths by age, all of which give quite similar numbers, combined with life expectancy tables (in this case from Statistics Canada).  

The US population therefore, in just 4 months time has had about 1.5 million years of life lost from COVID-19 (probably an underestimate), which is about as many years of life lost as from all the murders in the US in 2 years' time.

Reference for murder YLL statistics:

Update:  through the course of 2020, there were about 375 000 COVID-related deaths in the US, representing over 4 million years of life lost, which is a similar impact on the population as 
all of the murders in over 5 years' time.