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car thefts in Avon and Somerset 1998
owners' birthdates
thefts
days
thefts/day
expected
May 21-June 21
811
32
25.34
762.5644
April 21-May 20
794
30
26.47
714.9041
June 22-July 23
785
32
24.53
762.5644
July 24-August 23
756
31
24.39
738.7342
March 21-April 20
754
31
24.32
738.7342
February 20-March 20
730
29
25.17
691.074
August 24-September 23
719
31
23.19
738.7342
December 23-January 20
696
29
24.00
691.074
September 24-October 22
686
29
23.66
691.074
January 21-February 19
671
30
22.37
714.9041
October 23-November 22
657
31
21.19
738.7342
November 23-December 22
639
30
21.30
714.9041
8698
365
23.83014
car thefts in Avon and Somerset 1998
owners' birthdates
thefts
days
thefts/day
expected
May 21-June 21
811
32
25.34
762.5644
April 21-May 20
794
30
26.47
714.9041
June 22-July 23
785
32
24.53
762.5644
July 24-August 23
756
31
24.39
738.7342
March 21-April 20
754
31
24.32
738.7342
February 20-March 20
730
29
25.17
691.074
August 24-September 23
719
31
23.19
738.7342
December 23-January 20
696
29
24.00
691.074
September 24-October 22
686
29
23.66
691.074
January 21-February 19
671
30
22.37
714.9041
October 23-November 22
657
31
21.19
738.7342
November 23-December 22
639
30
21.30
714.9041
8698
365
23.83014
car thefts in Avon and Somerset 1998
owners' birthdates
thefts
days
thefts/day
expected
May 21-June 21
811
32
25.34
762.5644
April 21-May 20
794
30
26.47
714.9041
June 22-July 23
785
32
24.53
762.5644
July 24-August 23
756
31
24.39
738.7342
March 21-April 20
754
31
24.32
738.7342
February 20-March 20
730
29
25.17
691.074
August 24-September 23
719
31
23.19
738.7342
December 23-January 20
696
29
24.00
691.074
September 24-October 22
686
29
23.66
691.074
January 21-February 19
671
30
22.37
714.9041
October 23-November 22
657
31
21.19
738.7342
November 23-December 22
639
30
21.30
714.9041
8698
365
23.83014
Texas Lotto Frequencies - 477 Draws
Frequency
52
48
44
40
36
32
28
24
20
16
12
8
4
Nu
m
be
r
80
70
60
50
40
30
20
10
0
Texas Lotto Frequencies - 477 Draws
Frequency
80
70
60
50
40
30
20
10
0
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52
Texas Lotto Frequencies - 477 Draws
Frequency
18
16
14
12
10
8
6
4
2
0
35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74
Case 1: Thalidomide
Thalidomide
C13H10N2O4
1. Prescribed to pregnant women to combat morning
sickness and as an aid to help them sleep.
Thalidomide
C13H10N2O4
1. Prescribed to pregnant women to combat morning
sickness and as an aid to help them sleep.
2. Sold from 1957 to 1961 in almost fifty countries.
Thalidomide
C13H10N2O4
1. Prescribed to pregnant women to combat morning
sickness and as an aid to help them sleep.
2. Sold from 1957 to 1961 in almost fifty countries.
3. Inadequate tests were performed to assess the
drug's safety: approximately 10,000 children were
born with severe malformities.
Testing:
1. Scientists could not find any antibiotic activity, or any
other encouraging effects, in mice and rats.
Testing:
1. Scientists could not find any antibiotic activity, or any
other encouraging effects, in mice and rats.
2. Seemed to be harmless: outrageously high doses did
not kill rodents, rabbits, cats, or dogs.
Testing:
1. Scientists could not find any antibiotic activity, or any
other encouraging effects, in mice and rats.
2. Seemed to be harmless: outrageously high doses did
not kill rodents, rabbits, cats, or dogs.
3. Although no anticonvulsant effect was found, patients
reported experiencing a deep sleep. Other patients said
they felt calming and soothing effects.
Testing:
1. Scientists could not find any antibiotic activity, or any
other encouraging effects, in mice and rats.
2. Seemed to be harmless: outrageously high doses did
not kill rodents, rabbits, cats, or dogs.
3. Although no anticonvulsant effect was found, patients
reported experiencing a deep sleep. Other patients said
they felt calming and soothing effects.
4. One author later said that “Thalidomide was introduced
by the method of Russian Roulette. Practically nothing
was known about the drug at the time of its marketing”.
An employee of Chemie Grünenthal brought home
samples of the new drug for his pregnant wife, and
ten months before thalidomide was put on the
market in Germany, on Christmas Day in 1956, their
child was born – without ears. Years later, the father
learned that his daughter was the first living victim
of the epidemic of thalidomide-induced infant
malformations and deaths.
Frances Oldham Kelsey, Ph.D., M.D.
Case 2: DES
DES
Diethylstilbestrol
C18H20O2
1. First synthesized in early 1938 by English
university research funded by the MRC (who had a
policy against patenting drugs discovered using
public funds).
DES
Diethylstilbestrol
C18H20O2
1. First synthesized in early 1938 by English
university research funded by the MRC (who had a
policy against patenting drugs discovered using
public funds).
2. It was inexpensive to synthesize (from coal tar),
and was produced by over 300 pharmaceutical
companies.
DES
Diethylstilbestrol
C18H20O2
1. First synthesized in early 1938 by English
university research funded by the MRC (who had a
policy against patenting drugs discovered using
public funds).
2. It was inexpensive to synthesize (from coal tar),
and was produced by over 300 pharmaceutical
companies.
3. Its price was kept low from the beginning by
competition.
DES
Diethylstilbestrol
C18H20O2
1. First synthesized in early 1938 by English
university research funded by the MRC (who had a
policy against patenting drugs discovered using
public funds).
2. It was inexpensive to synthesize (from coal tar),
and was produced by over 300 pharmaceutical
companies.
3. Its price was kept low from the beginning by
competition.
4. DES (in tablets up to 5 mg) was approved by the
FDA on September 19, 1941 for 4 indications:
gonorrheal vaginitis, atrophic vaginitis,
menopausal symptoms, and postpartum lactation
DES
Diethylstilbestrol
C18H20O2
5. In 1941, DES found to be the first effective drug
for treatment of metastatic prostate cancer.
DES
Diethylstilbestrol
C18H20O2
5. In 1941, DES found to be the first effective drug
for treatment of metastatic prostate cancer.
6. It was first prescribed by physicians to prevent
miscarriages (in women who had had previous
miscarriages) in the 1940s as an off-label use. On
July 1, 1947, the FDA approved use for
miscarriage.
DES
Diethylstilbestrol
C18H20O2
5. In 1941, DES found to be the first effective drug
for treatment of metastatic prostate cancer.
6. It was first prescribed by physicians to prevent
miscarriages (in women who had had previous
miscarriages) in the 1940s as an off-label use. On
July 1, 1947, the FDA approved use for
miscarriage.
7. In the US, an estimated 5-10 million persons were
exposed to DES during 1941-1971, including
women who were prescribed DES while pregnant
and the female and male children born of these
pregnancies.
DES
Diethylstilbestrol
C18H20O2
8. In 1960, DES was found to be more effective than
androgens in the treatment of advanced breast
cancer in postmenopausal women. DES was the
hormonal treatment of choice for advanced breast
cancer in postmenopausal women for two
decades.
DES
Diethylstilbestrol
C18H20O2
8. In 1960, DES was found to be more effective than
androgens in the treatment of advanced breast
cancer in postmenopausal women. DES was the
hormonal treatment of choice for advanced breast
cancer in postmenopausal women for two
decades.
9. In the 1990s, the only approved indications for
DES were treatment of advanced prostate cancer
and treatment of advanced breast cancer in
postmenopausal women.
DES
Diethylstilbestrol
C18H20O2
8. In 1960, DES was found to be more effective than
androgens in the treatment of advanced breast
cancer in postmenopausal women. DES was the
hormonal treatment of choice for advanced breast
cancer in postmenopausal women for two
decades.
9. In the 1990s, the only approved indications for
DES were treatment of advanced prostate cancer
and treatment of advanced breast cancer in
postmenopausal women.
10.The last remaining U.S. manufacturer of DES, Eli
Lilly, stopped making and marketing DES in 1997.
Testing
DES was originally considered effective and safe for
both the pregnant woman and the developing baby. A
double-blind study in 1953 of pregnant women
(unselected for history of miscarriage) was not
published until six years after DES received FDA
approval for prevention of miscarriage. Even though it
found that pregnant women given DES had just as
many miscarriages and premature deliveries as the
control group, DES continued to be aggressively
marketed and routinely prescribed (though in
decreasing frequency—sales peaked in 1953 and by
the late 1960s six of seven leading textbooks of
obstetrics said DES was ineffective at preventing
miscarriage).
Effects:
First generation:
Women prescribed DES while pregnant are at a modestly increased
risk for breast cancer.
Effects:
First generation:
Women prescribed DES while pregnant are at a modestly increased
risk for breast cancer.
Second generation:
A new study shows DES daughters as having a 2.5 fold increase in
breast cancer after age 40.
Women exposed to DES before birth (in the womb), known as DES
Daughters, are at an increased risk for clear cell
adenocarcinoma (CCA) of the vagina and cervix, reproductive
tract structural differences, pregnancy complications, infertility,
and auto-immune disorders. Although DES Daughters appear to
be at highest risk for clear cell cancer in their teens and early
20s, cases have been reported in DES Daughters in their 30s
and 40s.