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Refresher Course
For
J2J Fellows
XVII International AIDS Conference

Presenter: Bob Meyers, NPF & J2J

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Why are we doing this?
To make sure that all J2J
participants in Mexico City are on
a level playing field, with all other
J2Jers and all other journalists.

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We will look at HIV/AIDS
in three ways. As a …

• Medical/Scientific Issue
• Public Health Issue
• Medicine & Public Health compared for
the benefit of journalists

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Some basic definitions
• HIV – Human Immunodeficiency Virus
• AIDS – Acquired Immune Deficiency Syndrome
• Medicine – a focus on the individual
• Public health – a focus on populations
• Incidence – the number of new cases arising in a given population
in a given time
• Prevalence – the proportion of people with HIV at a specific point
in time; expressed as a %.

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Big footnotes
1. The following segment was written by Mark
Schoofs, one of the founders of J2J, in 2002,
and presented at the XIV International AIDS
Conference in Barcelona, July 4, 2002 (Mark
is now a reporter at The Wall Street
Journal)
2. Bob Meyers did some editing prior to the XVII
AIDS Conference in Mexico City, in 2008.

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HIV/AIDS
As A

Medical/Scientific
Issue

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What Does AIDS Do
In the Body?

• AIDS is a disease of the immune


system
• The immune system is a network of
cells and organs throughout the body
• HIV destroys the immune system.

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What Does AIDS Do
In the Body?
• HIV primarily attacks one type of cell that is
crucial to the immune system: The CD4 T-
helper cell
• After exposure the body cannot fight off
infections, and so it succumbs to “opportunistic
infections” such as TB, pneumonia, etc., which
is why AIDS is a syndrome.

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AIDS is caused by HIV,
the Human Immunodeficiency
Virus

Courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases


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In many ways
HIV acts like most other
viruses
And the immune system treats it
like any other virus

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But in a few crucial ways
HIV differs from other viruses
 When the immune system responds after
HIV attacks it, HIV turns the immune system
counter-attack to its own advantage
 This allows HIV to persist in the body for
years and finally destroy the immune system

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The immune system is a
network of organs and cells
• Mucosal barriers:
Vagina, rectum,
mouth.
• Lymphatic vessels:
the immune
system’s
bloodstream
• Lymph nodes &
GALT: cleansing
centers
• Thymus, spleen,
bone marrow etc. 14
Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
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Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
The immune system is complex
and interactive
• Immune-system cells detect invading viruses and
bacteria
• Immune system cells mobilize each other by:
– Direct cell-to-cell contact
– Excreting messenger molecules such as “cytokines”
• Immune system cells destroy invading viruses by:
– Excreting “antibodies” that snare free-floating virus
– Killing the body’s own cells that have been infected
– Excreting molecules such as “chemokines” that interfere
with viral replication

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Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
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The CD4+ T-helper Cell

• “CD4+” means that the cell displays


(“expresses”) a molecule on its surface called
“CD4”. HIV attaches to this molecule and, like a
lock and key, uses it to enter the cell.
• “Helper” means that this cell “helps” other parts
of the immune system do their job. If the immune
system is an orchestra, this cell is the conductor.
• “T” is short for “Thymus-derived” and is a type of
immune cell. There are other T-cells, such as
killer T-cells.
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HIV replicates in CD4 cells. Amount of
virus produced determines disease course

New virus
assembly

2-3 Days
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Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
New research suggests that …
• This time frame may be a matter of
HOURS, not days
– Which could be one factor in failure of recent
vaccine trials

– Inserted by Bob Meyers, 2008

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Typical Course of HIV infection

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Graph courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
Relationship Between CD4 and
Plasma HIV viral load
• AIDS is like a train
heading toward a
crash
• Viral load indicates
the speed of the train

• CD4 count indicates


the distance to the
crash

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CD4 Count
in Phases of HIV Infection

Incubation

Primary
Presymptomatic
CD4 cell count

AIDS

5-14 days 1-4 mo. 4-10 years 1-2 years 23


Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
The level of HIV in the blood
predicts disease course
Amount of Virus in Blood

Rapid Progression

Slow Progression

One year 24
Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Immune system detects HIV
and sounds the alarm

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At the cellular level…
• Macrophages and dendritic cells “eat” HIV
– “Macrophage” comes from “macro” for big and “phage” for eat.
So macrophages are “Big Eaters,” or scavenger cells
• These scavenger cells cut up the virus into fragments
called “antigens” or “epitopes”
• They “present” these viral fragments to other cells,
including CD4+ T-cells
– Each CD4+ T-cell can recognize only one epitope
– When it meets its particular epitope, the CD4 T-cell clones itself
into an army of identical cells
• These “activated” cells stimulate other immune-system
cells, such as B-cells, which make antibodies, and killer
T-cells, which kill infected cells

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Function of the CD4 T Cell

Macrophage, Dendritic Cell,


or other Antigen Presenting Cell
Promote B-cell Antibody
Response (also called
“Humoral” response)
Activated CD4
Cell
Promote Killer T-cells
(also called “CTL”
Resting CD4 short for “Cytotoxic
Cell T-Lymphocyte”)

Secrete ß Chemokines
Rantes
Mip 1 alpha
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Mip 1 ß
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
HIV prefers to infect
activated CD4 T-cells
• 93-99% of HIV infects activated CD4
cells, which are HIV’s favorite “food”
– HIV occasionally infects unactivated or
“resting” CD4 cells, where for years it can
hide from the immune system

• By activating CD4 cells to mobilize a


counterattack, the immune system is
actually “feeding” HIV
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Function of the CD4 T Cell
after infection

Macrophage, Dendritic Cell,


or other Antigen Presenting Cell
Promote B-cell Antibody
Response (also called
“Humoral” response)
Activated CD4
Cell
Promote Killer T-cells
(also called “CTL”
Resting CD4 short for “Cytotoxic
Cell T-Lymphocyte”)

Secrete ß Chemokines
Rantes
Mip 1 alpha
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Mip 1 ß
Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
(Pause)

Why are we spending


so much time on this
science stuff?
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So everyone will know
how complex this is
And so you will be able refute
anyone who claims HIV does not
cause AIDS

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How antibodies work

• Antibodies work by
binding to particular
fragments of HIV as
the virus floats in the
blood or lymph.
• These fragments are
called “epitopes.”
• When the antibody
binds to the epitope, it
“neutralizes” the virus,
rendering it harmless.
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Graphic (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Antibodies try to snare HIV

New virus
assembly
B cell

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Slide (slightly adapted) courtesy of Bruce D. Walker, Massachusetts General Hospital,
Harvard Medical School, Partners AIDS Research Center
But HIV eludes antibodies
• HIV is sheathed in an
“envelope”
– The envelope is the most
mutable part of HIV, so HIV
keeps changing its coat,
making it impossible for
antibodies to bind.
• HIV uses part of the
envelope to enter cells
– But these critical parts are
cloaked with carbohydrates
molecules. Antibodies
rarely bind effectively to
carbohydrates.

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Image from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
Killer T-cells
are “big guns” in viral infections

• Antibodies snare free-floating virus


• But viruses infiltrate cells
– They turn the cells into factories that churn out
thousands of copies of themselves
– Inside the cells, they are protected from antibodies
– HIV also mutates to escape the antibodies
• Killer T-cells kill cells that HIV has infected

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This is one scientific
reason that HIV is so
difficult to stop once it is
in the body
… and why AIDS is so difficult to
cure.
Look 

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HIV replicates mainly in lymph
tissue, the immune-system
stronghold

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Images from The National Cancer Institute, http://newscenter.cancer.gov/sciencebehind/immune/immune00.htm
Site of HIV Production and
Storage

Lymph tissue with HIV stained Close up of several cells in


to look bright. “Stars” are cells lymph tissue producing HIV
producing HIV.
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Photos and slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota
HIV in the lymph nodes
• The lymph nodes normally trap viruses in the lymphoid
“germinal centers” and cleanse the viruses from the body.
• The lymph nodes trap HIV, but doing so activates CD4 T-
cells. Therefore, lymph nodes provide “food” for HIV:
activated CD4+ T-cells.
• HIV prefers to be in the very place where the immune
system kills most other viruses. HIV sets up camp in the
immune system’s stronghold.
• But: The fight between HIV and the immune system is
balanced at a standoff for many years

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Slide courtesy of Anthony S. Fauci, National Institute of Allergy and Infectious Diseases
HIV destroys the lymph nodes
• HIV causes persistent lymph-node swelling, or
“lymphadenopathy,” one of the signs of HIV
infection.
• Chronic, long-lasting activation of the immune
system, combined with HIV’s disruption of the
normal immune regulation, causes physical
destruction of the lymph nodes.
• The lymph nodes can no longer trap and destroy
HIV. The “delicate balance” tips in favor of HIV.

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Lymph tissue in HIV-negative
and HIV-positive people

HIV-negative HIV-positive
person for 5 years, no
ARV treatment
Upper left-hand corner: round All “geographical”
germinal center surrounded features destroyed—no
by healthy mantle discernible germinal centers
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Photos and information courtesy of Timothy Schacker, University of Minnesota
The consequences of HIV
infection
• As HIV slowly wins the battle, the immune system
can no longer repel some infections.
– These are called “opportunistic infections” (OIs for short)
because they take the “opportunity” given to them by the
weakened immune system.
• These other infections are what kills people. HIV
itself does not (though it can cause dementia.)

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Antiretroviral drugs (ARVs)
attack HIV itself
• They stop HIV from replicating, but they do not
eradicate HIV from the body
• They allow the immune system to recover
– Not full immune reconstitution. Lymphoid tissue often
retains signs of damage; CD4 cells often don’t rise to
pre-HIV levels.
– But usually enough immune recovery to fight off most
infections.
• Therefore, ARVs take the place of drugs to
prevent or treat most OIs
• But antiretroviral drugs are expensive
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Antiretroviral drugs (ARVs) block
HIV’s assault on the CD4 T-cell
Macrophage, Dendritic Cell,
or other Antigen Presenting Cell
Promote B-cell Antibody
Response (also called
“Humoral” response)
Activated CD4
Cell
Promote Killer T-cells
(also called “CTL”
Resting CD4 short for “Cytotoxic
Cell T-Lymphocyte”)
ARVs
Secrete ß Chemokines
Rantes
Mip 1alpha
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Slide (slightly adapted) courtesy of Timothy Schacker, University of Minnesota. ARV graphic (slightly adapted) courtesy
Mip 1 ß
of Bruce D. Walker, Massachusetts General Hospital, Harvard Medical School, Partners AIDS Research Center
Lymph nodes in HIV-negative,
HIV-positive, and ARV-treated
patients

HIV-negative HIV-positive The same HIV-positive


person for 5 years, no patient after 6 months
ARV treatment on ARV treatment
Upper left-hand corner: All “geographical” Germinal centers discernible
Round “germinal center” features destroyed—no again but lack healthy
surrounded by healthy mantle discernible germinal centers surrounding mantle
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Photos and information courtesy of Timothy Schacker, University of Minnesota
Without ARVs, many non-HIV “OIs” can
be cured or prevented cheaply
• Tuberculosis • Can be prevented short-term
with INH. Cured with
combination antibiotics.
• Can be prevented with
• Pneumocystis Carinii Cotrimoxazole (Bactrim) and
Peumonia cured with that and other
antibiotics.

• Thrush (candidiasis) • Can be cured with fluconazole.

• Can be cured and prevented


• Cyrptococcal from recurring with
meningitis fluconzazole.

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(This ends Mark’s brilliant review
of HIV/AIDS)

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So why is there no
vaccine against,
or a cure for,
HIV/AIDS?

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Unfortunately, these are some
of the responses …
• The virus is incredibly complex and
operates in a way rarely seen before
• Theories about how HIV operates have all
had failings
• Drug development takes time, and is
expensive.
• When testing a new drug, the risk to the
individual trial patient must be weighed
against the hoped-for benefit
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So until medicine and
science can give us the
answer …
We have to look at ways to
prevent HIV infections & AIDS

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HIV/AIDS
As A

Public Health Issue

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Some basic definitions
• HIV – Human Immunodeficiency Virus
• AIDS – Acquired Immune Deficiency Syndrome
• Medicine – a focus on the individual
• Public health – a focus on populations
• Incidence – the number of new cases arising in a given population
in a given time
• Prevalence – the proportion of people with HIV at a specific point
in time; expressed as a %.

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Some basic definitions
• HIV – Human Immunodeficiency Virus
• AIDS – Acquired Immune Deficiency Syndrome
• Medicine – a focus on the individual
• Public health – a focus on populations
• Incidence – the number of new cases arising in a given population
in a given time
• Prevalence – the proportion of people with HIV at a specific point
in time; expressed as a %.

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A very informal way of
looking at HIV transmission

• You have to do something


• Or have something done to you
• To contract HIV

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Vulnerable People
• Women
– Especially in male-dominant cultures
– In war zones
– Sex workers
• Children
– students
• Medical workers
• Men in risky relationships

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Transmission
• Unprotected sexual contact
• IV drug use
• Unsafe clinical environment
• Mother-to-child transmission

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Vulnerable Groups
• Local communities
• National defense
• Migrant workers
• Agriculture
• Education

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If there is infection, these are
possible movements of HIV
• IDU or Sex worker
or Unknowingly
infected person
• Spouse or Partner
– Child (in utero)
• Blood contact
• Hospital environment
• Unknown

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Until we have a vaccine
or a cure …
We have to focus on prevention

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Personal Prevention
• Condoms – Male or female
• Microbicides
• Limited sexual partners
• Clean needles
• male circumcision, for adults

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Societal Prevention
• Developing of new drugs
– Distribution of those drugs
– Preventing mother-to-child transmission
• Development of Vaccines
• Sterile clinical environments
• Government & industry attitudes

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Medicine & Public Health

Compared for the


Benefit of Journalists

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Medicine Public Health

• Primary focus on • Primary focus on population


individual • Emphasis on prevention
• Diagnosis & treatment • Interventions aimed at
• Medical care environment, behavior,
lifestyle, medical care
• Social sciences as an • Social science as an integral
elective part of PH part of PH education
education • Laboratory & field work
• Laboratory & bedside

• (after H. Fineberg, 1990)

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Leading Causes of Death
In the United States
In the Year 1900 In the Year 2000
• Influenza

• Tobacco
Pneumonia

• Poor Diet and Physical
Tuberculosis
Inactivity
• Gastritis • Alcohol Consumption
• Heart Disease • Microbial Agents
• Cerebrovascular Diseases • Toxic Agents
• Chronic Nephritis • Motor Vehicle Crashes
• Accidents • Incidents involving Firearms
• Cancer and other Malignant • Sexual Behaviors
Tumors
• Illicit Use of Drugs
• Early Infancy Diseases
• Diphtheria
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Each of the following
pictures can be viewed …

• as a story of an individual
• Or as the story of community issue

• Or both

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And if you’re going to
view them as both, then
you need two more basic
definitions …

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Some basic definitions
• HIV – Human Immunodeficiency Virus
• AIDS – Acquired Immune Deficiency Syndrome
• Medicine – a focus on the individual
• Public health – a focus on populations
• Incidence – the number of new cases arising in a given population
in a given time
• Prevalence – the proportion of people with HIV at a specific point
in time; expressed as a %.

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Journalism Practice

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In the next four
days we’re going to
look at a lot of
issues, both as
journalists and as
concerned citizens...
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…But right now I
want to briefly
discuss this
question – do we as
journalists have a
special obligation to
cover HIV/AIDS?
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I believe that AIDS is
curable…
• Despite all the failed vaccine trials
• Despite the failed scientific interventions
• Despite the difficulties at prevention…

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HIV/AIDS is curable …

through education

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Journalists are educators…
• We research difficult situations
• We show people what we have learned
• We give them information
– so they can improve their lives
– so they can improve society

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Because we are educators,
and given …

• The size of the epidemic


• The potential for its growth
• The impact on society
• The impact on people

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And the fact that print, or
broadcast & online
journalists cover everything
from ….
• Poor people • Marginalized
• Rich people populations
• National defense • Sex workers
• Our country’s future

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Then I think we can
educate many
segments of the
population about what
we know.

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And I think that is why
we came here

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Thank you!

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Acknowledgements for
Mark Schoofs’ presentation
• Anthony S. Fauci & Greg Folkers, National
Institute of Allergy and Infectious Diseases
• Bruce D. Walker & Marylyn Addo,
Massachusetts General Hospital, Harvard
Medical School, Partners AIDS Research
Center
• Timothy Schacker, University of Minnesota
• Laurie Garrett, Newsday, & Omololu Falobi,
Journalists Against AIDS Nigeria
• Bob Meyers & Nena Uche, National Press
Foundation
• The Wall Street Journal & The Village Voice 87
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