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The seasonality of pandemic and non-pandemic influenzas: the roles of solar
radiation and vitamin D
Asta Juzeniene
a,
*, Li-Wei Ma
a
, Mateusz Kwitniewski
a
, Georgy A. Polev
a
, Zoya Lagunova
a
,
Arne Dahlback
b
, Johan Moan
a,b
a
Department of Radiation Biology, Institute for Cancer Research, the Norwegian Radium Hospital, Oslo University Hospital, Montebello, N-0310 Oslo, Norway
b
Institute of Physics, University of Oslo, Blindern, Oslo, Norway
1. Introduction
Nearly all human diseases related to respiratory pathogens
exhibit seasonal variations.
1,2
However, the reasons for this
seasonality are still not known. Among the tested hypotheses
are: seasonality of low temperatures, absolute humidity (aerosol
transmission), or of dry air, crowding together indoors during the
winter, travel patterns, vacations, seasonality of ultraviolet (UV)
radiation from the sun that might kill pathogens, circannual
rhythms of hormones, such as the ‘dark hormone’ melatonin,
etc.
1,3–8
Another founded hypothesis is that seasonal variations in
UVB radiation and consequently vitamin D photosynthesis,
causing seasonal variations in vitamin D status,
9,10
which plays
a role in the immune response to infections, may be responsible for
the influenza seasonality.
9–15
Additionally, the question of
whether it is the host or the virus/bacterium that exhibits
seasonality arises. However, there are exceptions from seasonality,
notably for pandemic influenzas, which often occur outside the
winter influenza seasons. Furthermore, in equatorial regions the
seasonal pattern is weak.
2,16
In the present work we have compared the seasonality of cases
and deaths caused by both pandemic and non-pandemic
influenzas with doses of UVB radiation (vitamin D photosynthesis).
Influenza may cause death either directly (due to a primary
complication caused by the influenza virus) or indirectly (due to
secondary non-influenza complications either pulmonary or non-
pulmonary in nature).
17,18
Recent studies have indicated that the
majority of deaths in previous influenza pandemics have been a
result of secondary bacterial pneumonias.
18–21
In this paper all
deaths related to influenza are referred to as ‘influenza deaths’
without further specification.
2. Materials and methods
2.1. Influenza cases and deaths
Data from various sources were used in the present study
(Figures 1–6). The numbers of weekly Russian influenza cases in
Sweden (Figure 1) are from the publication by Skog et al.
22
The
monthly death cases from influenza in Norway during 1980–1999
International Journal of Infectious Diseases 14 (2010) e1099–e1105
ARTICLE INFO
Article history:
Received 30 April 2010
Received in revised form 8 August 2010
Accepted 1 September 2010
Corresponding Editor: William Cameron,
Ottawa, Canada
Keywords:
Influenza
Solar radiation
Vitamin D
Seasonality
Immune effects
SUMMARY
Objectives:
Seasonal variations in ultraviolet B (UVB) radiation cause seasonal variations in vitamin D
status. This may influence immune responses and play a role in the seasonality of influenza.
Methods: Pandemic and non-pandemic influenzas in Sweden, Norway, the USA, Singapore, and Japan
were studied. Weekly/monthly influenza incidence and death rates were evaluated in view of monthly
UVB fluences.
Results: Non-pandemic influenzas mostly occur in the winter season in temperate regions. UVB
calculations show that at high latitudes very little, if any, vitamin D is produced in the skin during the
winter. Even at 268N (Okinawa) there is about four times more UVB during the summer than during the
winter. In tropical regions there are two minor peaks in vitamin D photosynthesis, and practically no
seasonality of influenza. Pandemics may start with a wave in an arbitrary season, while seconda rywa ves
often occur the following winter. Thus, it appears that a low vitamin D status may play a significant role
in most influenzas.
Conclusions: In temperate latitudes even pandemic influenzas often show a clear seasonality. The data
support the hypothesis that high fluences of UVB radiation (vitamin D level), as occur in the summer, act
in a protective manner with respect to influenza.
ß2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
* Corresponding author. Tel.: +47 22934260; fax: +47 22781207.
E-mail address: asta.juzeniene@rr-research.no (A. Juzeniene).
Contents lists available at ScienceDirect
International Journal of Infectious Diseases
journal homepage: www.elsevier.com/locate/ijid
1201-9712/$36.00 – see front matter ß2010 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.ijid.2010.09.002
(Figure 2) are from the publication by Moan et al.
14
The weekly
death rates of the Spanish flu in some American cities (Figure 3)
were obtained from the work of Britten.
23
Monthly death rates
from 10 non-pandemic and two pandemic influenza seasons in the
USA during 1941–1976 (Figure 4) are from the publication by
Doshi.
24
The pattern of monthly influenza cases in Okinawa from
2001 to 2007 (Figure 6) are from Suzuki et al.,
25
while the data for
Singapore from 1990 to 1994 (Figure 5) are from the publication by
Chew et al.
26
2.2. Solar exposure and seasonal vitamin D synthesis in human skin
The main factors influencing UV irradiance at ground level are
solar zenith angle (variable with season, latitude, and time of day),
cloud and snow cover, aerosols, and the thickness of the ozone
layer.
27
In this study, global solar UV irradiances were calculated
using a radiative transfer model.
28,29
Daily total ozone amounts
used in this model were measured by the Total Ozone Mapping
Spectrometer (TOMS) onboard the Earth Probe satellite. The daily
cloud cover used in our model was derived from reflectivity
measurements by TOMS. The errors in ozone derived from TOMS
instruments onboard several satellites are generally less than
2%.
30,31
Not included in our calculations were atmospheric
aerosols, which may potentially have an impact on the solar
irradiance reaching the earth’s surface.
32–34
The calculated monthly UV exposures were based on the
satellite measurements in the period 1997–2004. A cylinder
geometry of the human body was used. The arguments for such a
choice have been presented previously.
35,36
Results are presented as vitamin D-forming UV doses. The
efficiency spectrum for vitamin D production gives the relative
effectiveness of solar radiation at different wavelengths in
converting 7-dehydrocholesterol (7-DHC) to previtamin D. An
efficiency spectrum is calculated by multiplying the intensity of
the solar radiation (wavelength by wavelength) with the action
spectrum for vitamin D production for the corresponding
[(Figure_1)TD$FIG]
Figure 1. Numbers of infected persons (&) per Thiessen area in Sweden for each
week from 1889 to 1890 during the Russian flu, obtained from Skog et al.
22
Weekly
photosynthesis of vitamin D (—*—) for a relevant latitude (Oslo, 608N) was
calculated by use of the vitamin D action spectrum, UV measurements, and
radiative transfer calculations (see Materials and methods).
[(Figure_2)TD$FIG]
Figure 2. The monthly influenza deaths (&) from 1980 to 1999 in Norway,
extracted from Moan et al.
14
Monthly photosynthesis of vitamin D (—*—) for Oslo
(608N) was calculated by use of the vitamin D action spectrum, UV measurements,
and radiative transfer calculations (see Materials and methods).
[(Figure_3)TD$FIG]
Figure 3. Weekly Spanish influenza death rates in Baltimore (398N), Augusta (338N),
and San Francisco (378N) from 1918 to 1919, taken from Britten.
23
[(Figure_4)TD$FIG]
Figure 4. The monthly death rates from two pandemic (A) and 10 non-pandemic (B
and C) influenza seasons in the USA during 1941–1976; data from Doshi.
24
Monthly
photosynthesis of vitamin D for San Francisco (378N) and Baltimore (398N) was
calculated by use of the vitamin D action spectrum, UV measurements, and
radiative transfer calculations (see Materials and methods).
A. Juzeniene et al. / International Journal of Infectious Diseases 14 (2010) e1099–e1105
e1100
wavelength. The vitamin D action spectrum was taken from the
publication of Galkin and Terentskaya,
37
and is similar to that
measured by MacLaughlin et al. in ex vivo skin specimens.
38
This
action spectrum is being used by a large number of investigators,
but is not ideal.
3. Results and discussion
3.1. Pandemic and non-pandemic influenzas
There are three types of influenza virus: influenza A virus,
influenza B virus, and influenza C virus.
39
Influenza A viruses are
the most important because they generally cause severe secondary
diseases and often cause seasonal epidemics and pandemics.
40,41
Influenza B is less common than influenza A, but can periodically
cause large epidemics, although not pandemics.
40
Influenza C virus
is less common than influenza A and B, and diseases caused by this
species are generally much milder; it is not thought to cause
epidemics.
40,42
Influenzas mainly attack weaker persons in a
population, such as children, the elderly, and the immune
incompetent.
39
The best known and documented influenza pandemics are the
Russian flu (1889–1890, about 1 million deaths), the Spanish flu
(1918–1919, about 50 million deaths worldwide), the Asian flu
(1957–1958, about 2 million deaths worldwide), and the Hong
Kong flu (1968–1969 about 0.7 million deaths worldwide).
43,44
In
April 2009, a novel H1N1 influenza A virus, the so-called pandemic
H1N1/09 virus (swine influenza, Mexican flu, North American flu)
was identified in Mexico.
45–47
The virus has since spread
throughout the world and has caused an influenza pandemic,
but it has not exhibited unusually high pathogenecity.
21
The full
impact of the current pandemic is not yet clear.
47,48
According to
the World Health Organization (WHO), more than 209 countries
have reported laboratory confirmed cases of pandemic influenza
H1N1 2009, and there have been at least 14 142 deaths.
49
The spread of Russian pandemic influenza, caused by the
influenza A virus subtype H2N2, was extremely rapid. The Russian
flu was first detected in Bokara (Central Asia) in May 1889, quickly
reached St Petersburg in October, and 6 weeks later was registered
in the UK.
22,44,50
In mid-December 1889 the flu was reported in
North America and in North and South Africa; in February 1890 it
was reported in Latin America and in Asia and in March in New
Zealand, Australia, and East Africa.
43,51
In Sweden, Russian flu
occurred in the winter, with maximal numbers of infected persons
between mid-December 1889 and late January 1890 (Figure 1),
22
almost coinciding in time with the seasonal (non-pandemic)
influenza deaths in Norway (Figure 2).
14
We can conclude that in
temperate latitudes even pandemic influenzas may appear with a
clear winter seasonality of incidence and mortality.
The Spanish flu, caused by influenza A virus subtype H1N1, is
sometimes referred to as ‘the mother of all pandemics’, because
since 1919 almost all influenza A pandemics have been caused by
descendants of this virus.
52
It is still uncertain whether the first
wave of the Spanish flu occurred in Europe or in America.
44,53–55
The first wave of the pandemic in European countries was in the
spring and summer of 1918. It was highly contagious, but caused
few deaths.
56
The second and largest peak was the most serious
and occurred in October 1918.
56
The third, most long-lasting
pandemic wave started in February 1919.
56
Influenza-related
mortality rates were high, ranging from 0.2 to 11 deaths per 1000
inhabitants in European countries.
56
In the USA, the first wave of the Spanish flu occurred in March
1918.
52,55,57
The second lethal wave peaked in the autumn of 1918,
and was responsible for most of the deaths, just as in Europe.
However, in Europe, only one autumn wave was seen in most
cities, whereas many of the USA cities had two peaks of mortality,
spaced by only a few weeks (Figure 3).
58
The second wave probably
spread from the east coast to the west coast, because the highest
death rates were registered on October 19 in Baltimore (398N,
768W), on October 26 in Augusta (338N, 818W), and on November 5
in San Francisco (378N, 1228W) (Figure 3).
23
The third wave came
in the classical influenza season (Figure 3).
23
In Baltimore the
winter wave was weak and came later, while in the other cities it
came in mid-January (Figure 3), i.e., when the vitamin D
photosynthesis rate is at its minimum (Figure 4A). One possible
mechanism explaining the differences in death rates between the
summer, autumn and winter waves of the Spanish flu could be
related to serum vitamin D levels and pre-existing heterosubtypic
immunity, probably induced by prior exposure to different
subtypes of influenza.
59
However, this pattern of three waves was not universal:
Australia, for example, due to the partial success of a maritime
quarantine that delayed the outbreak until early in 1919,
experienced a single, longer wave of influenza activity.
60–62
The
Spanish flu came in two waves in Singapore (18N), a tropical island
city-state: in June–July and in October–November 1918,
63,64
i.e.,
later than the first wave in Europe and in the USA.
Arguments for the role of UVB and vitamin D in Spanish flu in
the USA have been reviewed previously.
15
The lowest pneumonia
and influenza mortality rates were seen in the areas with the
highest solar UVB irradiance and lowest latitudes (these being
good indicators for high levels of vitamin D), while the highest
[(Figure_5)TD$FIG]
Figure 5. The pattern of mean monthly influenza A cases (&) from 1990 to 1994 in
Singapore; data from Chew et al.
26
Monthly photosynthesis of vitamin D (—*—) for
Singapore (18N) was calculated by use of the vitamin D action spectrum, UV
measurements, and radiative transfer calculations (see Materials and methods).
[(Figure_6)TD$FIG]
Figure 6. The mean number of monthly influenza cases (&) from 2001 to 2007 in
Okinawa, adapted from Suzuki et al.
25
Monthly photosynthesis of vitamin D (—*—)
for Okinawa (268N) was calculated by use of the vitamin D action spectrum, UV
measurements, and radiative transfer calculations (see Materials and methods).
A. Juzeniene et al. / International Journal of Infectious Diseases 14 (2010) e1099–e1105
e1101
rates were in the areas with the lowest UVB irradiance and highest
latitudes (indicators of low vitamin D levels).
15
The Asian pandemic influenza originated in the southwest of
China in February 1957 (i.e., in the influenza season).
2
It reached
Hong Kong in April, and then spread rapidly to Singapore, Taiwan,
and Japan. The causative agent, an influenza A H2N2 virus, was first
isolated in Japan in May 1957. This virus was found in June 1957 in
the UK and in July 1957 in the USA, but the peak of influenza
incidence and mortality occurred in October 1957.
2,54,65
This first
wave of disease in North America and in Europe was followed by a
second wave in January–February 1958, again in the influenza
season.
2,54,65
The Hong Kong influenza A virus subtype H3N2 was first
isolated in Hong Kong in July 1968, and in September it was
registered in Japan, the USA, England and Wales; it was registered
in France in January 1969.
66
Despite the rapid and extensive spread
of this virus, its impact was not the same in all geographical
regions: in North America, the majority of influenza-related deaths
occurred during the first pandemic season ((1968/1969), while in
Europe most deaths occurred during the second pandemic season
(1969/1970). The highest rates of influenza cases and mortality
were observed during the winter in all studied countries (the USA,
Canada, England and Wales, France, Japan, and Australia).
66,67
Thus, these two pandemics, the Asian flu and the Hong Kong flu,
followed an almost classical trend with high winter death rates,
similar to non-pandemic seasonal influenzas in the USA (Figure 4,B
and C).
24
Both of these pandemics occurred in Singapore, which has
almost no incidence variations in seasonal influenzas (see
below).
64,68
The Asian influenza pandemic in Singapore started
in May 1957 (earlier than in the USA, Figure 4A), and the Hong
Kong influenza pandemic first occurred in August–early Septem-
ber 1968 (also earlier than in the USA, Figure 4A).
64
All seasonal influenzas in the period from 1941 to 1976 in the
USA followed a similar winter trend, with the exceptions of the
1946–1947 and the 1975–1976 waves, which came late, peaking in
March–April (Figure 4, B and C).
24
However, these waves also came
before the vitamin D levels start to increase after the winter
(Figure 4A).
3.2. Seasonal variations in vitamin D photosynthesis and non-
pandemics
The monthly variations in vitamin D photosynthesis in human
skin in some selected countries were calculated using the action
spectrum of Galkin and Terentskaya
37
and assuming cylinder
geometry.
35,36
As shown in our earlier studies of the Nordic
countries,
69
the vitamin D level is maximal about a month after the
time of maximal rate of synthesis, which occurs close to
midsummer. This is due to the fact that the vitamin D level here
is determined as the concentration of 25-hydroxyvitamin D in
serum, and that the formation of this metabolite from previtamin
D, via vitamin D (mainly in the liver), takes around one week.
70
Above 378latitude, very low UVB fluences reach the ground during
the months of November through February.
71
Therefore, very little,
if any, vitamin D is produced in the skin during the winter. In fact,
the lowest vitamin D levels are found in February–March.
71
Seasonal variations in vitamin D photosynthesis decrease as the
equator is approached (Figure 5). In fact, as the curve for Singapore
(18N) shows (Figure 5), there are two minor maxima per year,
located almost symmetrically around the midsummer minimum.
The reasons why the symmetry is not complete are the slight ozone
asymmetry and changes in cloud cover, which were both taken
into account when we calculated the curves in Figure 5. November
and December are the months of the rainy season in Singapore. In
this city there is almost no seasonality of influenza,
26,64,72
as might
be expected from the small seasonal variation in vitamin D
photosynthesis (Figure 5). However, a small seasonal variation in
influenza has been observed, with small peaks in June and
December–January.
26,64,72
It appears that the influenza waves start
during periods of low vitamin D photosynthesis. These peaks may
be related to humidity, or possibly to contamination from seasonal
influenzas in the southern and northern hemisphere, and to the
seasonal variation in vitamin D photosynthesis (Figure 5).
For the subtropical region, influenza data are available for
Okinawa (268N) and Taiwan (238N).
25,73
In both of these places
there is a regular, major outbreak of influenza in the winter and a
minor outbreak in the summer. This pattern is also characteristic of
influenza circulation in other subtropical areas.
74
In these places
there is significant vitamin D photosynthesis throughout the year,
but it should be noted that the winter rate is only a fourth of the
summer rate (Figure 6).
In the USA, non-pandemics of influenza typically start during
the fall or winter months, but the peak of activity occurs in
January–March (Figure 4), just as we have found for Norway
(Figure 2). In both countries, very few cases are registered in the
summer time. Seasonal variations in immune system responses
have been reported in humans
75
and such variations may be
responsible for the increased incidence of infectious diseases
during winter and for the seasonality of non-pandemic influenza.
Vitamin D modulates the immune system, essentially strengthen-
ing it, in several ways, as reviewed elsewhere.
76–80
Norway is located between 60 and 708N, while the center of
population gravity of the USA is located between 35 and 458N. The
seasonal variations in vitamin D photosynthesis are larger for
Norway than for the USA (Figures 2 and 4). Thus, in the USA, as in
Norway, the numbers of deaths are small in the season when
vitamin D status is best.
3.3. Mechanisms behind seasonality
Being the main source of vitamin D, UVB radiation may affect
influenza via the immune system. It was demonstrated in two
independent studies
81,82
that children who were regularly exposed
to artificial UVB radiation had around two times lower incidence
rates of upper respiratory tract infections, influenza, and sore
throat than non-exposed children, and the phagocytic activity of
macrophages increased significantly in all exposed subjects in a
dose-dependent manner.
The impact of rurality on morbidity and mortality from the
1918 pandemic influenza in England, Wales, New Zealand, and
Japan was investigated.
83–85
The influenza morbidity in villages
was higher than or similar to that in towns and cities, while the
mortality appeared to be lowest in villages, revealing significant
differences compared to all cities and towns. The differences in
mortality rates between urban and rural regions may be related to
many factors, including differences in vitamin D status. People
living in rural areas have significantly higher vitamin D levels
compared to those living in urban areas.
86,87
3.4. Seasonal variations in host immunity or in pathogen virulence
An argument for the seasonal effect on the host are that
outbreaks of genetically similar strains occur simultaneously at
similar latitudes across different continents.
1
There seems to be, in
many cases, a continuous presence of pathogens throughout the
year.
88
Circadian variations of hormones, like melatonin, change
with the season.
88,89
This may lead to a seasonal variation in
immunity.
89
Thus, mice exhibit circadian variations of suscepti-
bility to pathogens, with the highest susceptibility in the
morning.
90
The same virus strain appears to be present in the hosts over
longer periods, two years or more, but leading to manifest disease
A. Juzeniene et al. / International Journal of Infectious Diseases 14 (2010) e1099–e1105
e1102
only under favorable conditions, mainly related to host immune
weakening.
88
One might expect variations in the immune system
to play a major role. The preventive effect of vitamin D
supplementation against influenza has also been demonstrated
in intervention studies.
11
Furthermore, Ginde et al.
91
found that
serum levels of vitamin D were inversely associated with upper
respiratory tract infections.
UV radiation interacts with the immune system in several ways,
as already mentioned. We believe that the main mechanism
involves vitamin D photosynthesis in the skin.
3.5. The influence of vitamin D on the immune response
Vitamin D plays an important immunomodulatory function in
primates. Deficiency has been linked with several autoimmune
diseases, the development of cancer, and an increased risk of
infection.
92–96
Better knowledge of the mechanisms through
which vitamin D regulates immune responses is essential for
understanding how it may prevent or reduce the impact of an
influenza pandemic in humans. Calcitriol, the metabolically active
form of vitamin D, influences host immunity in two different
important ways: generally it suppresses adaptive immunity,
particularly Th1 cellular immune responses, while it stimulates
innate non-specific immunity.
97
Vitamin D strengthens innate non-specific immunity in several
different ways. It up-regulates the expression of antimicrobial
proteins (AMPs) like cathelicidins or
b
-defensins.
98,99
The
synthesis of LL-37 antimicrobial peptide (the only human member
of the cathelicidin family, an important component of innate
defense) in human macrophages is one of the best known
mechanisms involving vitamin D.
98
In addition to its antimicrobial
properties, it is also effective against viruses, including influenza
virus.
100–102
Moreover, vitamin D induces the production of NF-
k
B
transcription factor inhibitor – I
k
B
a
.
103
The inhibition of NF-
k
B
signaling may impair influenza virus infection. Nimmerjahn
et al.
104
showed that human cells with low NF-
k
B activity were
resistant to influenza virus infection.
Other non-specific components of innate immunity regulated
by calcitriol are Toll-like receptors (TLRs) that recognize structur-
ally conserved molecules derived from microorganisms such as
bacteria, viruses, and fungi, and activate immune responses once
an antigen is recognized.
105
TLR signaling is strictly linked with
vitamin D. Influenza A is a single-stranded (ss)RNA virus. (ss)RNA
is a TLR7/8 ligand.
106,107
Furthermore, it can induce expression of
the gene coding for the LL-37 peptide.
102
While vitamin D may strengthen innate, non-specific immune
responses and possibly reduce the risk of influenza virus infection,
attenuation of adaptive immune responses might be linked with
decreased mortality.
9
Calcitriol down-regulates secretion of
proinflammatory cytokines and up-regulates the release of anti-
inflammatory cytokines, hence influences the Th1/Th2 bal-
ance.
108,109
Moreover, it suppresses antigen presentation by
antigen presenting cells (APC) like dendritic cells (DCs) and
macrophages.
110,111
The mortality caused by the highly pathogenic
influenza A virus strains appears to be related to the release of pro-
inflammatory mediators.
112
Thus, the attenuation of the Th1
immune response by vitamin D might be beneficial for infected
patients.
3.6. Use of vitamin D supplementation to prevent influenza
Solar radiation contributes significantly to vitamin D status. In
temperate regions vitamin D levels are higher in late summer than
in late winter, when the solar radiation contains too little UVB to
synthesize enough vitamin D in human skin. Cannell et al.
9,10
hypothesized that wintertime vitamin D insufficiency may explain
seasonal variation in influenza. Two preliminary studies support
this hypothesis.
11,113
A randomized controlled trial of bone loss in
postmenopausal, black women found that women given vitamin D
(800 IU/day) were three times less likely to report cold and flu
symptoms than controls given a placebo.
11
The intake of high doses
of vitamin D (2000 IU/day) for 1 year efficiently protected women
against the ‘typical’ winter colds and influenza, since only one
patient reported these symptoms.
11
Another randomized, double-
blind, placebo-controlled trial, comparing vitamin D supplements
with placebo in schoolchildren, found that intake of vitamin D
(1200 IU/day) during winter and early spring can reduce the
incidence of seasonal influenza A by a factor of around two, while
this is not true for influenza B.
113
4. Conclusions
Non-pandemic influenzas usually arrive in winter/early spring,
while the initial wave of pandemic influenzas may occur in any
season, but with secondary waves in midwinter. Seasonal waves of
all influenzas are small at low latitudes. It seems likely that
seasonal variations in the incidence and death rates of both
pandemic and non-pandemic influenza are related to seasonal
variations in vitamin D status. An argument against this hypothesis
might be that influenza death rates start to increase almost 2
months after the vitamin D levels have reached their minimum.
Similarly, the death rates start to decrease several months before
vitamin D levels start to increase significantly. This is likely to be
related to the generation of immunity.
Conflict of interest
We have no personal or financial conflict of interest to declare
and have not entered into any agreement that could interfere with
our access to the data on the research, or upon our ability to
analyze the data independently, to prepare this manuscript, and to
publish it.
Acknowledgements
Direct overpass TOMS data were provided by NASA/GSFC.
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