The Circadian Clock and Shift Work in the 21st Century

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>>Dr. Sandra Charles: Okay,
well good morning and welcome to our special session
on the circadian clock, talking about people
who do shift work. And actually when we were
setting up the flyer for this, I asked the young lady. I said, okay, you write that
the circadian clock and then when we input the subject
we’ll say, sleep rhythm, so nobody gets off put by it. So, but as Tomoko,
Dr. Steen mentioned, it’s a very important topic. It’s become really and I’m happy to see Austin police
officers here because they certainly can
personally attest to the impact of shiftwork on function
and just general well-being and we have several other groups
of people, some are people work in IT here at the library
would have that same problem. Some of our architects
of the Capitol, employees who are
here around the clock. And just in general, some of the
other people have a big problem with it and actually present a
public health issue are people like in the transportation
industry, who drive around the clock, and
then they try to make up time but then they have to stop. And it just creates
a big problem. So I know Dr. Smolensky is going to just address all
these issues for us. And just bring us up
to that up to date on what what it really does
mean for us going forward and the impact that it has on
our lives and our functioning. So I’m very happy to welcome
you, Dr. Charles, as I said, the chief of the
Health Services Division and the library’s physician
and I’m always so happy to have these speakers to
welcome Dr. Steven and I from science technology
and business. We collaborate on
these programs. And they have been so very
welcome and so very informative. And I get to live vicariously through her various
international meetings and rubbing shoulders with
various Nobel laureates. And I just think
that’s wonderful. And from a library point of
view, you know, we have so much in our collections about
these different topics. And we are trying to bring to
our employees as much as we can of what’s going on around the
— actually effects of whether or not they’re aware of it. So this is indeed
a pleasure for me. So I will ask Dr. Steen
to introduce our speaker, and we’ll get the ball rolling. So thank you again for coming.>>Dr. Tomoko Steen: Before
we introduce the speakers, I like to mention that we had a
successful two events in August and one was the health
fair and how to manage pain and also the lecture
by Professor Murray from Georgetown Medical School
and she talked about how to manage pain with
alternative medicine way. And as I mentioned earlier, so
there is a Nobel Prize was given on this topic, but
probably you know, not too many people know what
the exactly circadian clock is. And we are so lucky to have
you know, great translator of the circadian
clock to talk to us. And you know, he is very busy
but so he just gave a talk at FDA and came here also. So, we are we’re very fortunate. Professor Smolensky is
currently at the Department of Bioengineering at UT
Medical School, Austin. And he had a several decades
of work at UT Medical School, Houston Public Health
Department. And he moved to Austin. And he saw that he’s retired but he’s continued a very active
work from a variety of topics, including, you know, bio
monitoring type of work as well. So, after this, if you have
some questions off camera, maybe you can ask a question. So, and he’s really indeed
polymers and he worked on a variety of projects,
including, you know, climate impact to your health
and as well as toxic effect on your health and so on. And today’s topic
is circadian clock and shift work in
the 21st century. So how we, you know, this
is an old concept from 1800. But now, you know, with
more ever busy lifestyle in how we manage it, that’s
he’s going to talk about. So before further ado, please join me welcoming
Professor Smolensky [applause].>>Professor Michael Smolensky:
Well, thank you very much. Can you hear me back? Okay. Thanks for both of you
for the kind introduction and how let me just say I’ve
been working in this area for longer than I want to
say but at least 50 years and I didn’t set out to be a
chronal biologists the person who studies biological
rhythms, but it came to me because of various
problems that I came upon in doing my own medical research
as well as dealing with people in industry and so forth. So I’d like to share with you
some of the how should I say, concerns that we have
in dealing with people who do shift work or
non-standard work. And so today I’ll do my best to
give an introduction or overview and meaningful one of
the health and psycho, psycho social challenges
of doing shift work. And the first question
is what is shift work? And this particular slide that
I took off the internet shows that there can be seven types
of different shift work. Perhaps most of you
may be familiar with the fixed day shift where
you go every day to work, and work between eight
or nine and five and six, and that’s a day shift. But there are also a
great deal of individuals who work fixed night
shifts, so they are active. They’re sleeping during the day and they’re working
throughout the night time. There’s also flex time shifts. There are people who
will come in and work in a flexible work schedule that may not always
be during the daytime. It may be in the evening hours. And at times it may be during
the overnight hours as need be, both by the choice of the
employee or the employer. And then there’s the home
workers, which are more and more the case
with the millennials, but also all generations now,
where instead of people going out and leaving the house
and going to a workplace, they can work in their pajamas,
starting at four in the morning, have breakfast, take coffee,
whatever and unfortunately, continue to work into the late
hours or early morning hours and those who are in
the business world and have interactions with
people in different time zones and Europe or Asia are actually
doing a kind of shift work without even leaving their
own apartment or residence. Then you have the bottom
row, annualize hours. This is a so Australia Slide
where people have to get in a certain number of hours. And so they may pile them
up at hours during the night and so forth and
not during the day. And then probably the
most popular shift is the rotating shifts. Those are usually but not
always eight hour shifts. And generally, we talk about
the morning shift that may go from anywhere from 6am
to maybe three or 230 or so forth with a break. Then there’s the
afternoon shift that follows and then there’s the overnight
graveyard shift is some people like to refer to it. And then it gets
even more complicated because you have people
who rotate from mornings to afternoons to nights,
which is more biological because as Dr. Steen spoke
about the biological clock that was identified, most
people inherit a clock that runs with a cyclic periodicity
A little bit longer than 24.0 hours. So it makes it easier us for us
to stay awake late at night or, or shift our biological clock
and rhythms for later start time as we shift from
days to afternoons and evening, that’s
more biologic. But then there are other shifts
that are backward rotations where you go from working days,
then graveyard, then afternoons and that’s usually more
difficult to adjust to. Biologically. Then you have part time shifts and this is a perhaps
a misnomer here. It’s more like a split shift. For example. Bus drivers in in big cities, some proportion work,
two shifts. They may work from
five, five to 9am. Then they go home,
and then they may that is the morning rush hour and then they work
the night rush hour. The same thing goes for
school bus drivers that drive in the morning and evening. So they work they have
may work eight hours, we get paid for eight
hours a day. But they have a split shift
and the same thing goes for restaurant workers. Sometimes they’re working
the breakfast and the dinner. And so they don’t
work straight shifts, it’s kind of a part
time shifts and it gets into the not only the
early morning hours, but the nighttime hours. And then you have those
who are reserve workers. And so the military, they
could be standby workers, depending on the industry. And they may be brought
in at any time of the day anytime in the night. So there’s this to give you some
ideas of the different kinds of shifts and with
different psycho social and health concerns
for each type. So what are the some of the upcoming work
shift work schedules? Well, I’ve already talked about
the fixed eight hour shifts and the can be forward
and backwards. There are some people
who work 10 hour shifts. They may work four 10 hour
shifts and get three days of. Some of these shifts came out
of the petrochemical industry where the idea was to with union
and management negotiations, where people could put
their workplace together and then have time for family
and other hobbies and so forth. Unfortunately, the 12 hour
shifts that are the next row, the 10, 12 hour shifts, we saw
people getting second jobs. So they were even getting more
fatigue and more health risks and psychosocial compromises. And then, we see in the
petrochemical industry in particular and also in
nursing more and more now is that individuals may
work a sole 24 hour shift or consecutive 24 hour
shifts without any real rest. For example, in the
Houston Ship Channel where we have tankers coming
in, they have to be turned around to be filled up again. They have to be cleaned out
for gathering or shipping in other types of products. So there’s a whole cadre of
workforce that go in and work in sometimes under very
hot conditions for 24, almost 48 hour straight hours to
get those holes cleaned and turn that ship around,
because time is money. Then I already talked
about the split shift and the flex time
employee depending on with the employer
and employee workout. So the question is why do we
even think about shift work? Well, in the old olden
times, we had the bakers, we had the security people which
we have representatives here, night guardsmen, watchman
What have you which were in small number but work
the night shift to repair that keep things safe in terms
of security and then the bakers. They have the food’s ready
and so forth for the people who needed to buy it when
it was ready to buy it at the store in the morning. So we but nowadays, we have
the critical services that need around the clock
manning or womening. The police, we have
representatives important. The firefighters, the military,
the healthcare industry, utility industry,
transportation, this was mentioned are
some of the key ones that operate on a 24 hour basis. And then we have the
manufacturing processes that are like continuous processes,
production lines, it’s not cost efficient
to shut them down. So they have to be maintained
usually around the clock for much more than eight hours,
usually the full 24 hours. So we need people
to be on the line to for the continuous
production process. And that’s because the machinery
is so expensive that we need to have people using it or
also becomes prohibitive for the products to be
purchased and company to make a decent profit. And then you have
support services for other shifts workers. You can also talk about
the hotel industry, the casino industry,
resort industry. Nowadays you got
the Lyft drivers, the Uber drivers,
the taxicab drivers. So it’s almost nowadays fairly
uncommon not to find people who are not doing standard
work, which we would call nine to five kind of hours for work. So I’ve kind of gone into this. Some of the other
industries that didn’t fit on the other slide
are the public, would put in the
ambulance personnel the correctional personnel. I’ve already mentioned the
staff hotels, motels, casinos, construction services. We have so many people using
our roadways during the daytime, that more and more contract work
on either constructing roads or winding roads or repairing
roads are done during the nighttime and that’s heavy
physical work being done at a biological time
if you will. The bakery as I mentioned
earlier, also grocery stockers, Targets and other
Wal-Marts and so forth. When you go to the store
during the daytime, how do you think
things get on the shelf? That’s, that’s the night crew. You I’ve mentioned the
school city bus drivers, and the restaurant staff. Another big shift work category
are the media, television, radio and other media,
the people who come on in the morning to
give you your weather and the overnight news are
generally reporting to work about four in the morning, which means if they
have a transportation, they’re up at 230,
3 in the morning. They have a completely
different social life as well with their family
and their friends and that becomes problematic. So basically, we have
also as I said earlier, more and more people who are
working at home and doing kind of a self-imposed nonstandard
work schedule or kind of shift schedule because
the hours may not be the same from one day to another. And I know Tomoko has talked
about having to interact with some conference that’s
going on in Asia and I to have had to give remote
talks for conferences, conferences of several days in
Australia, which required me to be alive and functional
and cognitively sharp at two to three o’clock in the morning,
which is quite difficult. So that’s becoming more and
more common with connectivity that there’s more
and more people who are working strange hours. So what is the actual labor
force involvement in shift work? And this is really hard
to know on nowadays. These data came out
probably about 10 years ago. So they’re antiquated
data and because we have so many people now who are
working at home and are kind of doing assume shift work, so
there are approximate figures. So in the USA, about 14 to 20%
of employees have some type of what I call nonstandard
work schedule that is not nine to five am. And what’s interesting is
in the USA, less than 30% of the population that are
workers are following a five day workweek, with a
fixed day schedule of less than 40 hours a week. So that means most
people are working more than more than 40 hours. And they’re working more
than five days a week and they may not be working
only during the daytime. The European Union is
interesting because only 40 — I know the economy’s bad right
now in New York, but only 24% of the workforce is actually
involved in in a kind of a work schedule
that that has exemption from doing weekend
work or being exempted from doing fixed night work
or doing rotating shiftwork or working less than
10 hours a day or working more than
40 hours a week. So we have a lot of our employed
people who are not working nine to five that we really
assume they are. And in developing countries,
this is really an underestimate. 15 to 30% of the
labor force is engaged in either fixed night work
or rotating shift work, and that includes even
school children and teenagers of developing nations. For example, in Brazil, a large
proportion or I won’t say large but a fairly large
proportion of teenagers, because their families are
poor are working late nights or even night shifts. And in Brazil and San Paulo,
they actually have schools that are shift schools so kids
who are working nights can go to school when they should
be sleeping during the day or late night depending on
what schedule they’re working. So it affects all age
groups, both men and women and It’s really part of
our everyday life now. So why do people work shifts? Well, many people say it’s
the nature of the job. It’s a continuous process job
and you want to make a living and you have no other
opportunities. That’s what you’re going to do. And many people choose
it voluntarily because they find it’s
better arrangements for the family or
child childcare. You have a to work or family
could be the wife is working shift work and the
guy’s working day shift, so they can really rearrange
and have a better interaction with either elderly
or young children. Sometimes it’s the only
available job given the person’s training educational level, and sometimes it’s a personal
preference preference. There are some people
who are born with a biological clock
that’s really odd. They call them night
owls or they’re larks. They like to the night
owls like to stay up late and they have a different
kind of personality. They may prefer to do
the night work shift and not the day shift. Then you have the other people
on the other end who are larks and they prefer to get up
very early in the morning as part of their biology. And they like to work the
very early morning shift and not the night. So there are many reasons. Sometimes they’re overlapping so
that people who, who like, yeah, people say they love
the night shift. They love the shift work and
they ask them some questions and they can’t tell
you what day it is. So not everybody
can do shift work and not everybody
should do shift work. individuals who have rather
severe sleep disorders that compromise the quality
of the sleep are likely to have more problems
doing night work and rotating shift work. individuals who have diabetes
who require a careful diet, what you eat and when you eat as
well as the medication schedule, Shift work makes
it very difficult because when you’re working
during the night shift, you’re eating at the really the
worst biological time you could ever think of, in terms
of diabetic conditions. People who have epilepsy,
and really require and severe more severe forms, require a very tight medication
scheduled to be seizure free and not have seizures
around machinery. Doing a rotational shift work or fixed a night work
can be problematic. Individuals with
coronary heart disease, or vascular disease
is problematic because of the extra
stress in doing night work and sleep deprivation and
we’ll talk about later. Certain psychiatric disorders
especially melancholy or mood depression. Because altered sleep, the sleep
wake cycle is tied very closely into good mental
health and those who are already compromised,
can actually precipitate anxiety or severe depressive episodes and other medication I should
say other medical conditions requiring precise medication
or meal timing regimens, probably those people
should think second or third time consideration
before going in the shift work. So, when doing night,
fixed night and rotating work
schedules that require that they require a
special biological and social accommodation. And these are just a few. It has to have a person who
can tolerate biologically the continual alteration of
the sleep wake schedule. It sounds really fundamental,
it sounds really easy. It’s not easy, especially
as we age. Our sleep wake schedule
becomes less and less flex, flexible and more fixed. Includes tolerance
so jetlag symptoms, even though you’re not
getting in a jet airplane and flying over time zones. You’re doing kind of a if
you will, a social jetlag. You’re, you’re changing
your sleep wake cycle, as if you are traveling
from Washington DC to London or France every week
back and forth. And that gets pretty old fast and it takes a little
while to adjust. The circadian we
call a time structure or 24 hour rhythm time structure
does not adjust right away. It takes sometimes a week. So people may be adjusting by
the end of their night shift, only to then go back
to a day shift. And then they’re
going back and forth. And some there may be
some accommodation, biological accommodations or
a acclimatization to that kind of schedule with time
but we’re not sure if that really does occur. There’s the ability
people have to be able to tolerate frequent sleep
deprivation, short sleeps, sometimes it’s short, it’s
for six hours in the shift day from the rest of the
shift day that first night with the experiencing
of excessive fatigue. And how to deal with that. And it depends on the kind
of job, if you’re nursing and medicine or your exact
type of job where you have to have good reflexes make
good decisions and what to do in the real world scenario. Working the night shift is,
I’ll talk a little bit later, is that a time of real slow
decision making reaction time and, and working memory issues. And so we’re not the same. We don’t have the same
capacity to make decisions. We don’t have the same cognitive
reasoning skills that we do. Not just because
we’re sleep deprived, but because our circadian
rhythms govern even how we, how we learn how we
think and how we react and how what processes
are called efficiently. Then there’s the issue of
you mentioned the cognitive and physical performance
stress and a typical time when we should be asleep
but we’re now found at work and I mentioned earlier,
meal consumption at a typical biological times in many industries really
don’t even have cafeterias to choose decent food
from their machines. A lot of carbohydrates,
a lot of bad yuck. And actually what happens when people are doing
the night shift, I don’t think it’s
well recognized and they’re sleep deprived. The biology has a
compromise response and it has it motivates our, our brain to seek
carbohydrate rich foods and snacking behavior. So if we actually, we
actually did studies on people working the night
shift versus the day shift. And it’s like a rodent
in the field. They just and snacking on
carbohydrates either brought in the lunch box or their
own food bag or they’re going to the vendors, vendor
machines and buying snack foods which are not really healthy. And the other problems is really
the difficult work life balance pressures, people who have
families, children, wife, elderly parents, having enough
time to do the job at night, and they’re getting at home
and supposed to be sleeping to be able to do your job. But then there’s social events
going on, sporting events, have family members expect to have some interactions
or they need them. And it’s really, it
takes a special person to adjust to that. So I don’t want to go
into a lot of detail about the biological clock was
discussed in the introduction. And we inherit a biological
clock in our brain. It’s called a superchiasmatic
nucleus. It’s not very big. And it has neural
connections to the pineal gland which secretes the
hormone melatonin. Melatonin, you can get over
the counter these days, but it’s produced
biologically only at night. And melatonin does many things. It helps us sleep at night,
but it also protects us from inflammatory conditions and
free radicals and it also helps to fight precancerous
conditions. And this whole clock system is
synchronized for our ancestors by the time of daylight
alternating with darkness. So sunrise and sunset for
our ancestors was, hey, that’s when we’re active. We’re diurnal reactive species. And when the sun goes down,
melatonin comes up and it says, hey, it’s time to go to bed
and melatonin circulating all over the body and says to
all of our organ processes, our brain functions and
our cells saying, hey, slow down, it’s nighttime. It’s time to rest and repair. So when we’re doing shift
work, we’re seeing light at different times of the
day and night artificially, especially at night
artificial light with our electric
light practices. And that plays havoc
with our biological clock and the production of melatonin. And we’ll talk about the
consequences of that. So in reality, what
we have is if we look around the room we have
a biologic biology that’s organized in space and left you
see a nice anatomy with organs, lungs, etc. And on the right
we have a, an organization of our biology in time
as biological rhythms. So 24 hours I won’t go into
metzo or monthly rhythms and annual rhythms and
other period rhythms. I’ll restrict to
talk just to 24 hours to keep it straightforward. And if you start measuring, and
taking blood samples and measure for melatonin, and you can see
the tremendous variability, and melatonin is a hormone. The bottom row shows plasma
cortisol that’s another hormone produced by the adrenal
cortex that is important for our dealing with
stress, physical and mental Also metabolic
functions. And then even core temperature, our body temperature shows a
nice circadian rhythm in spite of the temperatures showing a
98.6 if you live in America, or I think it’s 98.8 if you
live in the UK and Europe, so what I’m saying is our
biology is really well organized in time. And it’s synchronized
in it’s phasing. So we’re very efficient
in space and time and when you do shift work, all of a sudden you’ve turned
not your physical anatomy upside down, but your biology
upside down. And that is really
the crux of jetlag. So if you took a circular clock
diagram, and this is quite a bit of information, but it’s just to
be illustrative, and you looked at the normal sleep at night,
wake span during the day, and we just indicated
at different times like a clock function, that
peak time of various variables that just to give
you an illustration, what things are peaking
when during the 24 hours and how you get an idea of
how we’re organized in time. But if you do rotating
shift work, all of a sudden all
this gets messed up, because each biological
function doesn’t shift with the same rate constant. Each biological function
has its own rate function. So you get everything
disorganized and you have a really
inefficient biology during the adjustment phase. So the real problem is then is that when we’re doing the usual
work situation, let’s say nine to five, we’re coincide with the
natural diurnal activity span, in sync if you will,
with the normal circadian time organization. So here you have the bottom
waking time corresponding to work on the above panel and then you have
sleep that’s off time. And that’s really
nice because it fits in with our circadian
rhythms structure. So the problem again comes in
when we’re doing shift work and that includes a night domain where you have then people
during the night indicated by the upper bar and
black background working. And that’s now awake time. And off time is now during the
daytime when you’re supposed to be sleeping after
you get into that shift, and then the circadian
rhythms are scrambled. So just to give you a
quick demonstration, this is a study done
in Minnesota, it’s only a matter of one. But here’s the plasmic cortisol
rhythm of 57 day shift nurses and medical technologists. And in this case, one night
shift volunteer who is willing to undergo blood tests at
regular intervals and you see that the whole rhythm
for the night shift work and worker is completely
reversed for this function, as is the lymphocyte
white cell function. So everything is reversed
on a adjustable person, an adjusted person
to the night shift. So that gets us to the
real crux of why I’m here. What is the consequences
of people doing shift work, whether they’re doing
it for an employer, or whether they’re doing it
for themselves working at home, in self-employment or if
you will, even working for an employer but
working in one’s home? So there are short-term issues. I don’t know if you’d
call them real health. Their be acute effects would be
some people get disorientated, they can fatigue they
have health problems. Usually minor ones, but the type of health problems are
usually problems with — got a indigestion problems with
constipation, things like that. Sometimes short sleep,
interrupted sleep with fatigue and more longer term effects
are going to be effects on increased risk
for heart disease. Both because of doing
shift work and also because of poor nutritional
habits that accompany it and very often shift workers
also tend to smoke and all kinds of things that add together. Gastrointestinal disorders. Peptic ulcer used
to be a common, common problem with
shift workers. Now that you can get
over the counter Pepcid and other other other
medications, it’s not so much a problem. Sleep, as I mentioned over
and over as a major problems, psychological effects
especially depression is common and also anxiety,
and also effects on preexisting conditions
that will be aggravated. Social effects are inhibited
interactions with family and friends, especially under the conditions
of sleep deprivation. Very often things
get pretty tense, especially with adolescent
children, who, with a tired father and mother
who’s worked already 12 hours on the night shift
comes home to deal with an adolescent
who has a on issues. You’ve got problems
and it’s common, and also that the adolescents
are kind of free ranging when single family parents
are doing shift work, because they get
away with things because they know what’s going
on when they have free time and when nobody’s watching. And then there are
issues about lifestyle and community activities
that are that are restrictive
in that kind of work. So the shift work
schedules compromise sleep, and it really results
in sick can result in significant sleep
deprivation. And this slide, not
meant to give you graphs, but it just shows that
the sleep duration between two successive shifts
of the same time or rest days for 297 workers and so
between two successive shifts in this particular industry that
was studied, the average amount of sleep was six hours. That was the average for the
workforce, but it was as little as two or three hours
for some people. And as much as seven
hours for some. When working the night shift, the early morning shifts
was a little better. But the afternoon shift was
more like the rest shift because people can have a more
normal circadian time structure and a more normal
life, if you will. So one of the big
problems when I was younger and doing some shiftwork
research on nurses, I would actually walk
through the hospital floors. I had nothing else
to do with my life. I became a shift worker. So I go through it 2, 3,
4 o’clock in the morning in the Health Science
Center in Houston and in the teaching hospital, and this really was
the situation. I’m not saying that all
nurses are this way, don’t get me wrong. But it’s a hard life. It’s a demanding life and in
the United States unlike certain other countries, we don’t like to pay people
for sleeping at work. But really, some other
countries are using fatigue mitigation strategies. Just like the airlines use it in
transatlantic and transpacific where they have time to go back
and sleep in a provided area. Several industries and
overseas are actually allowing individuals on the
night shift to have time for power naps or what have you. And that’s probably
that is a good idea. So some of the problems
in shiftwork, the shift work caused
chronic sleep deprivation and the consequences of
that is increasing the risk, increasing the risk
for insulin resistance and what does that mean? That means the risk of developing metabolic
syndrome and diabetes. It’s also a big risk
factor would be associated that with impaired
glucose regulation. And because people who are doing
night work often either fixed shifts or rotation shifts, and eating at an really a
typical biological time, there’s increased risk for
obesity, and it’s not well known but a lot of circadian rhythms
studies have been done looking at not only what you eat, but
when you eat and there’s a lot of fad diets and you
should break up your meals and have little meals
throughout this awakening span. I don’t necessarily advocate
that because in our studies, both on rodents and humans,
I use us for example, the human study was
using army rations where you were given the
subjects all the army rations to eat as a breakfast
every day for one month and nothing else during the rest
of the 24 hours or another flip of that arm of that study,
eat the same army rations which are not too tasty, but
always as a late dinner meal. So when people were taking the
army rations and eating them for the month for the breakfast, people maintained their
weight or lost weight. There’s about 2400, 2800
calories, women and men. And when they took the same army
rations and ate them at bedtime, everybody gained weight. So because of the circadian
rhythm organization, foodstuffs are handled
differently. When you eat them in the
morning, they’re broken down. They’re not stored. They’re used for
fuel for the day. When you eat your meals late
in the day, or overnight when you should be sleepin,. that’s stored. That’s gained. That’s body weight gain. So a calorie is not
a calorie in terms of body weight maintenance. So a lot of shifts
workers, firemen, policemen, truck drivers, I’ve not seen
a lot of really skinny ones, and this It’s not their fault. It’s what they have
to do with I’m sorry, that’s what they have to do. There also is the issues of these conditions
favoring them the development of cardiovascular
disease, both directly from the unusual work
schedule and secondarily, from the metabolic alterations
and the food pattern of eating. And then there’s a high
risk from developing cancers and men prostate cancer
and women breast cancer, endometrial cancer, men
and women colon cancer, colorectal cancer comes
back to that as well. And certain other acute and
chronic medical conditions. More and more, we’re finding
now some liver pathology because of unusual
eating pattern secondary to develop metabolic syndrome
and type two diabetes. And again, doing shiftwork. Especially with the night
component is a very high risk factor for work accidents
and injuries. And here’s one example. This is a study that I did
with a colleague at the School of Public Health in Houston
were we had a data database from Nebraska and their
workman’s comp workman’s compensation claim database. Looking at transportation,
accidental injuries, and here you see across
the bottom of the graph, time of day and military
fashion. So noon time is twelve hundred. Sixteen hundred is 4pm. Twenty hundred is 8pm. And you can see the night shift,
day shift and evening shift or afternoon shift, if you
will, labeled that the bottom and you see that the occurrence
of transportation accidents by workers who filed claims 1998 to 2002 is not randomly
distributed throughout the 24 hours but or by shift but you
see a preponderance of accidents that occur overnight, because
people make mistakes at night of judgment, leading
to severe accidents. I did a study of accidents due
to falling asleep at the wheel because not only
was I interested in fatigue related
accidents of truck drivers and passenger car drivers, but I
was also aware that people have to drive to and from
their night work. And before work,
it’s usually dark. And after work it may be sun
sunrise, but they’re fatigued. And so is there a pattern
and you can see quite clearly that the occurrence
of falling asleep at the wheel is no surprise is
greater during the overnight hours and you can ask
what is the relative risk? We actually did road
traffic density. So we’re talking about 10s of
thousands of order difference in risk of having an
accident overnight, relative risk overnight
compared to the afternoon hours. So even driving around at
the wrong time is a problem. Severity of accidents on varies
by time of day we were able to get information on the cost of medical care per
injury and workman’s comp. This is the difference
in your job title. And you can see and we’ve
reproduced these findings also in studying fireman, fireman who have accidents also
during the overnight work, graveyard work shift
because they’re called out for either ambulance work or firefighting just
like in this graph. They’re more severe or they’re
more costly than ones occur in the afternoon
or early evening. So why do these accidents
happen? Now certainly we have
sleep deprivation and people are fatigued, but there also are high
amplitude circadian rhythms in our ability to
perform cognitive tasks. Our brain is organized
in time and just to summarize this slide
very quickly, the magnitude of difference in our
ability to perform in terms of reaction time,
eye hand coordination and decision making
is equivalent to a blood alcohol
level about point 9% which is a low level
inebriation, if you will. And so and it’s also equivalent to ingesting a five milligram
hexobarbital sleeping pill. So we’re not talking
about trivial changes. So the in terms of those
individuals who have to make snap judgments in terms
of stress or whether they be in security, where
they’d be in firefighting, doing ambulance work or whatever
it may be military intelligence and the government,
the ability to perform at the wrong biological time
and decision making is a risk. And there are certain
people who have less peak to trough variation
over the 24 hours. And those are people
who are more appropriate for doing important shift work that involves important
decision making. And those people
can be selected out. We did some work on Navy Seals. And Navy Seals are
something else. They don’t show this type of
variability when they’re young. They’re pretty — we can give
up for 48 to 72 hours straight and do repeat and
measure testing on them. And the amount of variability
that they have over the 24 hours and over that 72 hours that
are sleep deprived and forced to perform military duties
is incredibly consistent, but those people are quite rare. We’re talking about run
in the mill individuals. Now, unfortunately, when you
look at the major disasters that had been reported
over time and some of us older people remember. Some of the younger
people may not, say what is he talking about? But the Three Mile Island
Nuclear Plant disaster happened on the night shift. It was a slow response. People didn’t notice and
didn’t react properly. The Chernobyl nuclear disaster
was also during the nighttime and it was not monitored
properly of some of the warning signs. Those of you are old enough,
there was a chemical leak in India and Gopal that
was incredibly deadly to the surrounding population that occurred during
the night shift. The Exxon Valdez oil spill,
which happened, I don’t know 15, 20 years ago now was the pilot
was operating in the middle of night under sleep deprivation
and made poor judgments and grounded and spilled
a great amount of oil and had incredible
ecological damage up in Alaska. The NASA Challenger launch
disaster actually had a component of a shift to work
problem with sleep deprivation. There were some individuals
who are on that launch team who actually felt that
we shouldn’t launch. Some of the people had missed
some key warning signs and some of them were too tired to
really want to launch a argument to support their concerns
and that was a looking at the report they
actually problem of the nighttime work schedule
being fatiguing leading to bad decision making. In our own work looking at
medical personnel working around the clock, medical
residents and nurses, the poor I hand coordination
related to self-sticks with needles, unprotected
needles for injecting is much more
common in the night shift, the person working the
night shift than day shift and as I already talked about highest rated worker
compensation injury events. I’m not watching my watch
so Tomoko, if I’m going to slow you speed me up, okay? Okay, so this slide has a
bunch of information on it. And I’ll just say that we can
separate the type of conditions that people are going to have. And not everybody has them. And it happens also as
a function of number of years or aging on a shift. By the way, if you’re young,
and you get in the shift work, and you just don’t like it
or you can’t tolerate it, you’re gone anywhere from three,
three months to two years, those people who continue to do shift work especially
difficult shift where are kind of self-selected, superstars. But they’re still prone to
having mental health effects and other biological
effects over time. So we see in the mental
health we see extra stress and anxiety I mentioned,
depression, becoming a little
neurotic, neurotic. Problems with vigilance. Burnout syndrome is
really common and usually around the age of 45 to 55
individuals who are tolerant to shift work for all
their early years, all of a sudden may
start to complain of having problems sleeping,
having digestive disorders, having how should
say anger expression, poor work performance, but
then they secondarily gets up poor self-esteem and they
no longer can do shift work. They have to leave and go
to a day shift and more and more industries
are recognizing that and shifting them and finding
replace time shift work. Cardiovascular disorders, the literature some literature
suggests a 40% increase risk for angina, coronary heart
disease, high blood pressure and risk for having a
myocardial infraction infarction and that it could
include also stroke. In women, the shifting, those who are not taking
birth control pills, shifting from days to
night can have effects on menstrual cycle duration
and length and for in that case of ovulation patterns
and in pregnant women who are doing shift work because
we don’t accept them exempt them from doing shift work. They can do it if they wish. Prematurity is more common as is
low birth weight and delivery. Brain effects I’ve
already went through. Sleep loss, reduction in
deep sleep, more fatigue, more break broken sleep
spans and continuous and one study reports
even reduce brain volume from doing shift work. More research needs
to be done there. I’ve mentioned gastrointestinal
disorders, distained digestion heartburn,
abdominal pain from constipation and or actually development
of peptic ulcer. And another nice word for
flatulence is just playing gas. Okay? And what’s most
concerning in recent years and the increased studies
finally epidemiologic wise in women increased
breast cancer in men and women colorectal cancer
as I mentioned before, and also a prostate
cancer in males. Now the other problem I
mentioned earlier that people who are working shifts very
often have medical conditions like take blood pressure
medicines, thyroid, what have you. And those of us who study
circadian rhythms like me, interested in the translational
part, I want to know if people take their
medication at different times, morning versus evenings, the
medications work differently. And it turns out a
whole lot of them do. So people who take the
popular drug valsartan, which is now a generic for
treating high blood pressure. Most doctors most people prefer
to take their medications at breakfast in the morning. But in reality, what
we’re starting to find is the most meaningful
indicator of one’s risk or for the diagnosis of
high pretension and the risk of having a stroke
or heart attack or developing coronary heart
disease is not your daytime blood pressure that’s measured
in the doctor’s clinic. But it’s your asleep
systolic high number, blood pressure mean. And people who work
shift work nights when they’re shift’s over, all of a sudden they have
an abnormally elevated blood pressure compared to when they
were sleeping the nights before. So that increases the
workload of the heart. It makes the risk for
cardiovascular disease higher. Sorry to say that it’s true. And then so very often
people develop hypertension from doing shift work because
of poor nutrition habits. Genetics is always there,
but also the work schedule. And people started
taking medications. Now if they always took
them when they woke up, now they’re maybe not only
waking up in the morning, now they’re waking up in
the middle of the night. And this slide shows that if
you take your medicine valsartan either at eight o’clock
in the morning, or in this case eight
o’clock at night, that there is different amounts
of blood pressure reduction at different times
a day according to how the drug behaves
so differently because of different
absorption distribution and hitting the targets
of the circadian system where the drug works at a
different biological time. So, in certain people,
this can mean loss of protection throughout
the full 24 hours. For some people that may
be producing hypotension, with side effects of
fatigue, dizziness and poor decision making. So this is another
problem with shiftwork. Now, getting to cancer. In the 1970s, I became
concerned about not only air and water pollution,
and noise pollution, but light pollution due to
artificial light practices and everybody thought
I was a nutball. Maybe I was I don’t know,
but, but at any rate, others had the same concern
doing independent work and one who has done a wonderful job is
a fellow whose name is Stevens, Richard Stevens, I think
he’s at in Connecticut. And he started looking at
the epidemiology of cancer in shift workers, as did Dr.
Sharon Harmer and her group at Harvard at School Public
Health and School of Medicine. And a number of studies have
shown that in nurses and also in women who are flight
attendants who do transatlantic and transpacific shifts, which
are really doing shift work, that they’re getting light at night Mother Nature did not
expect us to get any more light at night except from
stars and the full moon. And so just showing
us your studies, Hansen and why these studies
were done over in Europe. And basically it shows women who
are doing only night work have about a 50% on average
increase in risk for developing breast cancer
and nurses only about 30% and, and manage controls that
are also doing night work. Also, I should say that
those who are working more than six years, nurses are also
at very high risk and the study at the bottom also shows that
just cancers in general are of greater risk for people
who do shift work as a career for a long duration
over 30 years. It starts increasing it
year 15 of doing night work or rotating shifts work
which you see light at night. Again, remember that slide light
at night inhibits melatonin. Melatonin, got one minute? Okay, I have to hurry up. Okay, so a Melatonin
is inhibited, and so you have the loss
of protection of melatonin that prevents the
development of cancer. The same is true of
colorectal cancer, colon cancer and rectal cancer. It’s more common and it’s
also apparent more often after a threshold
of about 15 years. And then finally, just to
give you a brief overview of the cycle social issues
I’d have to go quickly fixed and night rotating
shifts work is complaints of insufficient time
for hobbies, inability to attend a
time social functions with family members
or on their own, difficulty attending
the daily needs. Daytime medical dental
appointments and all our doctors’
offices open another night, going shopping, banking,
investing, what have you, difficulty and inability
to attend daytime or evening children’s school
events or sporting events that most families would like to
do together, a total disruption of family life and with
the result often of discord between children, spouse and
worker, a lot of divorces that are occurring and inability
to attend to participate in favorite activities
and organized sports. So here you have a person asked
if he likes the work shift, he says, I work the night shift. How the hell do you want me to? How can you expect me to
be at the meeting at 2am. This is a cycle social issue. And then finally, we have
the circadian rhythm, biological clock issues
that I’ll skip this one is that people are exposed
in the workplace. Those who are exposed in
the chemical industries or in different environments, to things that Mother
Nature never thought that we would be exposed to. And so we have a different
biological vulnerability during the night biology, if you will,
versus the daytime biology. And so I’ve recently
just collected 100 papers or so showing dramatic
differences either in animal models or human
actual studies of differences in the risk for developing
toxic reactions, or severe reactions
more on the night shift, then on the day shift, and
also, very often, the conditions in the workplace are more I’ll
just say less clean, more toxic, because you have a
different kind of workforce, the other people more
oriented for the daytime that keep things clean. And during nighttime processing,
you don’t have the same staff. So you’re actually exposed
to higher concentrations, usually of things that can
cause adverse reactions and your biology is
less able to cope with them in the first place. So finally, as I say, around
the ages, I interrupted as I briefly mentioned earlier, that people who are really
good at doing shift work. And I should say a lot of people who are actually
biologically able to do shift work have
a different biology. We can talk about the strength
of the circadian time structure by the amplitude or
shift of each rhythm. And the total time
structure and people who can easily do shift
work and travel overseas, have a less strong lower
amplitude of variation. Those people can do shift work,
they can travel back and forth, and they don’t get much jet lag
until about the age of 45 or 50. And all of a sudden, as
we age, the provenance of our time structure
degrades anyway. And you get to the point where
then everything gets mixed up like you’re on
jetlag all the time. So people who are tolerant
to shift work all of a sudden at a later age finally
can’t do it anymore. They have a develop a very
severe shiftwork Sleep Disorder, they just can’t sleep. They have to go to a day
to day work or go back to a normal diurnal
activity schedule. They will not get better. They can try sleeping pills,
it doesn’t work very well. They have, as I said,
the work performance and I said earlier results
in lower self-esteem, they very often develop
a mood disorder, which is rather severe. And that leads to disturb
relations with family, friends and coworkers and they also
have digestive systems and at that time, they also
have diabetes and other metabolic conditions,
cardiovascular disease, and they just feel like hell,
so not everybody can do it. So in summary, human beings
are a diurnal species. They prefer to do work during
the daytime, and sleep at night. Why not? However, in
today’s modern society, we have continuous processing. We need security, we need
good people all around us. We need firefighters, ambulance
personnel, medical staff, and that requires that
we have people available to support society and societal
needs throughout the 24 hour time span and that
requires rotating and permanent night shift
work schedules that result in repeated disruption of our circadian
rhythms plus inhibition of melatonin secretion by light
at night exposure which can lead to all kinds of health
effects as I went into. So I’ve already said that in
summary we can have permanent night shift being associated
also rotating night shift being associated with radio acute
and chronic health effects. Reduce cognitive performance
and decision making when having to be called upon to make
very important decisions, sometimes life versus death
ones in the middle of the night and night shift will work poses
possible increase industrial toxicity risk, and then
consequences sleep deprivation coupled with lighting
that exposure. We need to do more research to
further understand the impact on actual shift workers
and also the new type of workers working at home. Will author now are
truly without knowing it, shift workers are night
workers in a fixed way. So I thank you for
your attention. I hope I can take
a few questions with the allotted time. Yes. Yep.>>Hi, [inaudible]. I’m here for my brother
who should be sleeping. He’s a shift worker. And he specifically asked me to ask is there any
[inaudible] studies like if you sleep three hours
and then later sleep four hours, like is that worse if he’s
having to break up his sleep? He’s also got a two year old.>>Dr. Michael Smolensky: Okay,
so Okay, so the question is, I think your, your fundamental
question is, is it best to try to get all your sleep in
one shift, if you will, or one continuous span,
or can you break it up? Well, let’s put it this way. If you can’t get a
continuous span of asleep, and that’s your only
option to break it up, then that’s better than nothing. However, what’s not realized
is during usual sleep is a lot of things happen
that are connected with a different sleep stages
with dreaming and light sleep. So under ordinary
conditions like people who are active during the
daytime and, and working nine to five shift but sleeping at
night, when you’re sleeping at night, the different
sleep stages are triggering, for example, in males, the
production of testosterone, its gating the hormones
that control blood pressure and differentiate hypertension
versus normal tension. During the nighttime,
normal nighttime span. our immune system is
activated to prepare us for our normal activity
span, thyroid hormone, the adrenal hormones
of stress and so forth. So by splitting up the sleep, you’re disrupting the other
higher frequency sleep rhythms that are tied to
supportive health functions that in the long term, come
back and haunt the shift worker who splits who is sleep
deprived and also has to break up their sleep schedule. Now mothers when they give birth
and fathers when they have, you know, kids at home,
that’s a short term issue. And that’s not a chronic
issue that can lead to long term negative effects. But in the case of the cancer,
melatonin if your brother does that for many years, the
increased risk for developing as a male a prostate cancer,
and depending on his genetics, colorectal cancer are real
factors and also I should say, arterial sclerosis and other
metabolic conditions including type two diabetes. Any other questions? Yes.>>I’ve seen a lot of things
lately, in fact, I into work and I saw this huge display
talking about [inaudible] –>>Dr. Michael Smolensky: The
question is about the econ — the question is about CBDs. How did you know that? Actually, there’s a
lot of talk about CBDs and CBDs is the I have a
very significant interest in that area. And with my colleague, we’re going to be starting
some real medical trial outcome trials with medical
doctors looking at treating medical conditions
of Alzheimer’s disease, Parkinson’s disease, ALS, and
because the CBDs are useful for modulating the immune
system and the nervous system and the inflammatory system and
we don’t know but we’re going to be doing CBD trials and we’re
going to be administering them at certain circadian times. Now with regard to your
question, individuals, young people who are doing night
work, I didn’t get time to go into it, but they can get
away with a lot of things that you can’t get
away on the day shift. So you have more drug of
abuse activities going on in the night shift. There’s more sexual
harassment that goes on during the night shift
and goes unreported. And you have more CBD use
and also THC use, and so, and other drugs of not
my choice, if you will. So, there are some real
issues that we need to sort out that are problems
for society in general, but because of this
shift work scenario, where people can
get away with things because there’s less
supervision. It’s problematic, not just CBDs,
but the whole scenario there. Any other, do you
gentlemen have any, yeah.>>I do have a question
about night shift. Is it better to have a
straight or fixed night shift versus the rotation and then the
effect of going back to sleeping at night on the days off?>>Dr. Michael Smolensky:
Yeah, okay. Okay, if you’re single and you
don’t have a lot of demands, a straight night shift is good. There’s a lot of people
who are introverts. They love the night shift. They don’t want to be
interacting with people, they don’t have that
personality. So they like to do their job. They do it well. They do it at night,
and when they go home, they want to they’re
not big social animals. They may not have a
family, and they can, they’re pretty regimented. If you’re that way you can
sleep and that’s really good. You minimize a lot
of these problems. Now, it when you’re rotating
going back and forth, that’s when things become
complicated because see when you’re sleeping
during the daytime like in a previous
scenario gave you, generally people will
darken their bedroom. So when they’re sleeping
during our daytime, it’s dark in the room. They’re biologically adjusted
to asleep by day work by night. So they have the normal
melatonin secretion in the daytime, which
is their nighttime now. And so there they don’t
have the cancer risk that the other rotating
shifts worker would have because they’re flip
flopping and getting light at the wrong biological time. And they’re also not disrupting
the other circadian rhythms which lead to other problems
with efficient nutrition and some of the other
medical conditions that can develop more easily with a disrupted circadian 24
hour time structure repeatedly over one’s lifetime. Have I answered your question?>>Yeah you have but I believe
you said fixed shift is better but what about on the days
off and then they go back to trying to sleep at night?>>Dr. Michael Smolensky:
That’s, that is tough. It depends how regimented it is. Even in college students
who are diurnally active and supposedly sleeping
at night. They like to party on the
weekends and so do young people. So they may go out
to restaurants, bars, sporting events where
there’s artificial light. The light is seen by the
eye, the signals transferred to the clock and melatonin
by timekeeping system. And that system thinks if
you’re partying Friday night and Saturday night, late
at night with light, they think that you
just took a flight from let’s say, Washington,
DC to LA. And then you got to get up
Monday morning if you got that you’re in a morning
shift and you say, oh, I feel like hell, yeah. Because your body
thinks you’re now in LA. You’re not Washington
going to work. So that’s what’s called the
social jetlag, and nowadays, you can get enough light from
your iPhone, iPad and TV, actually simulate enough light
that your biology thinks you’re in a different time zone is
consistently shifting you. And although I’ve talked about the homework are now
more doing type of shift work in the home environment,
we’re starting now with preschoolers giving
them iPads, kindergarteners, and they’re getting light. Kids are doing their homework
assignments off iPads at night, and they’re basically exposed
to kind of a night shift. And they have trouble
going to sleep. They’re sleep deprived, and
they don’t performance school as well. And I don’t know what will
be the health consequences in 20 years in terms of endocrine related
reproductive biology, tissue related cancers, I
have no idea but it’s scary. Very scary and also metabolic
disorders because when you when you’re tired, and
you can’t go to sleep, you have a biological
motivation to eat. I don’t know if you
feel that or not. I’ve actually I’ve done quite
a bit of research on this. So in fact, when we do around
the clock, medical studies on patients bring 20 in and
we have medical residents. I just go out and buy apple pie
is in all kinds of snack big because it’s all night long. They’re snacking
these young people. And that’s what happens
when you don’t get sleep. And that’s the way to
get instant nutrition, sugar breakdown to
keep the system going. And so with these kids that are
using these iPads, young adults, they are eating more
snack foods at night and not necessarily
healthy ones. So I kind of got off
the subject there. But it’s a it’s a some — it’s
an issue our society has to come to terms with the American
Medical Association has issued warnings. The National Toxicology
Program, NIOSH been working with and by the way, NIOSH
is really your go to government agency
for the shift work. Research and recommendations
are doing work on firefighters as well as policemen
and doctors and nurses. But we have a lot to learn. And I didn’t mention it, it’s
more of the blue spectrum of the total light that we see
that is most biologically active in inhibiting melatonin. And that is the spectrum
of the light that is most energy efficient. So we’re seeing more lights in,
in metropolitan areas in homes that are blue light spectrum,
and everybody’s saying, hey, look, we’re saving
the environment. Yeah we’re killing off the
human race but [laughter] and I didn’t go I
didn’t go into it but –>>Does it help to get
the glasses with the –>>Dr. Michael Smolensky:
Yeah, the glasses will help. Yeah, and that’s what some
people think is pretty phony but a quality there are glasses
that will shield the blue light and protect you’re very correct. And that can be helpful
to shift workers as well as regular people. I didn’t have time to mention
it, but I’ll take the time now. In young women who are not
taking birth control pills, light is a very important
factor in in controlling or influencing the length
of the menstrual cycle and out of the ovulation. And there actually
is a patent if you go through the library here on
the use of light, bedroom light for women who have very
abnormal long menstrual cycles and they’re infertile, they
can use a 75 watt light bulb on their bedstand overnight
on days 13 through 17 of their menstrual cycle and after two months can
almost normalize a very, very abnormal menstrual
cycle into normality and increase the probability of desired impregnation
consumption. So in the opposite
way, artificial light at the wrong times, can elongate
and disrupt menstrual cycles. And we’ve done some studies
on women living in caves without a light exposure
except special light that they put on when needed. Not rich and blue, and their
menstrual cycles are altered. And, and we’ve done
some other studies. So there’s a lot of lot of
things I didn’t have time to go into, but our
biology is, you know, we evolved in in an environment
that was very cyclic with light, dark patterns, noise and quiet,
cool and hot, what have you. And our biology has adapted to
the biological clock network to be synchronized
to the environment for optimal efficiency,
both in cognitive function, physical performance function,
and metabolic function. And Mother Nature, when
Edison created the light bulb, everybody said eureka, and all of a sudden society was
freed because, you know, when lights went down at night, what did you have
what was left to do? We had you can burn, make
a fire, use a gas lamp, not very powerful for reading,
didn’t have television, didn’t have iPads, didn’t
have iPhones, smartphones. And so, society became
very different. And so our experiences with
artificial light and electricity which made more prevalent
shiftwork because of continuous
process growth a society 24 hours society. We’ve only had really about four
to five generations of humans that have experienced so
called light at night. And abnormal eating. Our ancestors didn’t
eat at night. Our ancestors got up and they
went hunting, killed a squirrel and maybe ate berries. And, and our brain our
biology was organized that we store sugary moieties
in our liver called glycogen. So even before we wake up,
that glycogen is broken down and you start getting
sugar circulating because the clock knows you’re
going to get up you need to have some energy for
our ancestors had to go out and pick berries and do stuff. Well, when you’re doing shift
work, all that stuff is fouled up on the preparation for
optimal biological performance. So we don’t know what’s
going to be the end result. We’re seeing cancers. We’re seeing, obviously more
depression, mental disorders. And people with depression and certain other medical
disorders are highly influenced by light, light spectrum, as it
interacts with sleep, and sleep and mood are so tied together. We’re seeing a lot of mental
disease, I’m sure you see it as well, and you’re
having to deal with it. And so, we, we don’t know. This is a salient problem
that we take for granted. So light, it’s wonderful. Look what we can do as a
society, and that’s why I said, air, water and then I
got into light pollution. And I said, this guys,
but it’s everywhere. It’s most it’s one of the most
prevalent polluters in the world and it’s everywhere,
in your home, outside your home,
in your workplace. So anyway, I’m getting
the signal with the hook. All right, so really
thanks a lot for your interest
and your questions. Thank you.>>Dr. Sandra Charles: If
you have continued questions, you can come up after
the program but I’d just like to thank Dr.
Smolensky for that very, I would say erudite explanation
of the circadian [inaudible]. You’re raising a
lot of questions in my head and of a few people.>>Dr. Michael Smolensky: Okay. Thank you.>>Dr. Sandra Charles: We
expect you to come back. I want to hear about
that [inaudible] research and we definitely
need you to come back.

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