About Cloves

Physicians & Researchers

PIK3CA Related Conditions Research Network


In 2020, CLOVES Syndrome Community was awarded a $600,000, three year grant from the Chan Zuckerberg Initiative’s Rare As One Network.  This network is a group of 50 patient-led organizations that are accelerating research and driving progress in the fight against rare diseases. The Rare As One grant will provide CSC with capacity-building tools, resources, funding, training, and support, to strengthen our expanding patient community and scientific goals.


CLOVES Syndrome Community is working to create a patient-led collaborative research network in order to broaden the medical knowledge base, accelerate treatment options, and improve quality of life for people with CLOVES and PIK3CA Related Conditions.  

What is a collaborative research network and why should it be patient-led?

A patient-led collaborative research network pulls together a community of stakeholders – including people with specific diseases, their family members, researchers, and physicians – to discover and prioritize critical research questions. The research network relies on the collective voice to identify the most pressing questions and knowledge gaps about a disease. It then recruits the most qualified researchers to help answer these questions and to conduct these studies.  

Why patient-led? Patients are the heart and driving force behind CSC. We believe that patients and families are the experts in their life and their condition. We believe that no one is more motivated than patients to drive progress against their disease. We believe that there is power in collaboration and in breaking down systemic barriers. 

How are we going to get there?

CLOVES Syndrome Community has identified a series of milestones that will get us to our goal. 


✔Conducted  30+ stakeholder interviews to understand the research landscape

Reviewed published literature on CLOVES + PROS, and posting the links on our website

✔Created a slide deck of one-page summaries of each of the published papers

✔Built a drug repurposing database

✔Awarded $20,000 to Dr. Ralitsa Madsen, postdoctoral fellow in Professor Bart Vanhaesebroeck’s research group at University College London Cancer Institute for the project titled “The systems biology of activating PIK3CA mutations in mosaic endothelial cell models.”


Planned the first patient-led International Scientific Meeting for PIK3CA Related Conditions in October 2021, with over 300 attendees registered, and 33 abstracts submitted

Hired four part-time staff members

✔Collaborated on research tool development and research strategy

✔Awarded $10,000 to Dr. Bryan Sisk, Assistant Professor of Pediatric Hematology and Oncology at Bioethics Research Center research to support the study titled “Vascular anomalies communication” (VACOM)  

✔Awarded $25,000 to Ana Angulo-Urarte for the project titled “Identifying the molecular impact of PIK3CA variants in PROS towards stratification of patients and personalized medicine.” 

✔Awarded $25,000 to Dr. Robert Semple for the project titled “Human Pluripotent Stem Cells as a Model to Interrogate Pathogenesis and Developmental Origins of CLOVES”

Up Next

  • Bi-Monthly PIK3CA Related Conditions Research Roundtable
  • Research Gaps Analysis with Odylia Therapeutics
  • Patient Video Education/Awareness Project
  • Development of Patient Friendly Educational Materials About Research
  • Launch Patient Registry with NORD
  • Crowdsource and Prioritize Research Studies 
  • Organize CLOVES Management Guidelines meeting
  • Regularly disseminate information on the latest research and treatments.
  • Annual Research Grant RFP   

How can you help?

As the Collaborative Research Network progresses we will share additional ways to get involved, sign up here to stay up to date on new opportunities. 

We believe in the power of the collective. We believe that together, we can make a change in the lives of people with CLOVES and PIK3CA Related Conditions. 

Screening Guidelines


Clinical Practice Guidelines for CLOVES Syndrome – Vascular Anomalies Center, Boston Children’s Hospital

Imaging Guidelines for Vascular Anomalies developed by Children’s Hospital Boston – Guidelines for imaging with MRI, ultrasound, CT and angiogram when indicated.

Recommended Kidney Screening for children with CLOVES – Recommended screening guidelines for children with CLOVES, developed February 2012

The Vascular Anomalies Center team at Children’s Hospital Boston recently became aware of three cases of Wilms Tumor in young patients with CLOVES syndrome. While Wilms tumor has been associated with some overgrowth related disorders, such as Beckwith-Wiedemann Syndrome, it is a new finding in patients with CLOVES syndrome.

Our recommendation for Wilms tumor screening is serial ultrasounds performed every three months up to age 8 years after which there is not thought to be any increased risk of developing Wilms tumor. We have also chosen to notify families and physicians of CLOVES syndrome patients between the ages of 8 and 12 years so that they may decide whether to obtain a single ultrasound to rule out late development of Wilms tumor.

Questions may be addressed to your child’s pediatrician or to the Vascular Anomalies Center, Children’s Hospital Boston, at 617-355-5226.  

There are recent publications about Wilms Tumor in young patients with CLOVES syndrome. While Wilms tumor has been associated with some overgrowth related disorders, such as Beckwith-Wiedemann Syndrome, it is a new finding in patients with CLOVES syndrome.

Treatments & Trials


Unfortunately, there is no cure for CLOVES. Surgery and other types of medical interventions are the primary treatments for CLOVES overgrowth, vascular anomalies and other related medical issues. However there are many current opportunities for you to participate in research.

Please read below about research opportunities and new targeted treatment medications to treat CLOVES/PROS. 

Vascular Anomalies Family Planning Study

A researcher at Ohio University is recruiting female patients with vascular anomalies to participate in an interview about their experiences related to pregnancy, fertility, and family planning.

The direct link to the interest survey is:  

More details on the study

Repurposing Drugs Research

Physician researchers at the University of North Carolina School of Medicine and want to ask your help. They have a short survey which we hope to use to learn about old drugs that might help treat new problems, a process called drug repurposing. We are interested in repurposing drugs, herbal medicines and over the counter medicines. We are interested in finding new treatments for rare disorders such as what your group is interested in as well as common disorders such as obesity and mental illness.

Now Recruiting: Research Opportunity for people with Microcystic Lymphatic Malformations

This is a phase 2 clinical study in patients with microcystic LM.

This is an open label study (all patients participating in the study receive drug) for patients ages 13 and up who have a diagnosis of a microcystic LM.

For more information, click here.

If you are interested in participating in this study, complete the short survey below.

Now Recruiting: VACOM Study – Share your experience seeking medical care for Vascular Anomalies

This study is open to adult patients and caregivers over the age of 18, who live in the United States. Participants will receive $40 for their time. If you are interested, please complete this form. Contact Dr. Bryan Sisk with any questions at [email protected]

Study Assessing the Efficacy, Safety and PK of Alpelisib (BYL719) in Pediatric and Adult Patients With PIK3CA-related Overgrowth Spectrum

This is a prospective Phase II multi-center study with an upfront 16-week, randomized, double-blind, placebo-controlled period, and extension periods, to assess the efficacy, safety and pharmacokinetics of alpelisib in pediatric and adult participants with PIK3CA-related overgrowth spectrum (PROS). Enrollment is currently open in Norway, Spain, Germany, Switzerland and in the United States: UNC Chapel Hill, Washington University and UCLA.

Identification of Biomarkers for Patients with Vascular Anomalies 

Purpose: To identify biomarkers in patients diagnosed with a vascular anomaly*. 

Who is eligible: Any participant with a diagnosed vascular anomaly* that are currently not on treatment for the condition and are having labs (blood) drawn as standard of care.

*Vascular anomalies included: Generalized Lymphatic Anomaly (GLA), Gorham-Stout Disease (GSD), Kaposiform Hemangioendothelioma (KHE), Kaposiform Lymphangiomatosis (KLA), Klippel Trenaunay Syndrome (KT), Congenital Lipomatous Overgrowth, Vascular Malformations, and Epidermal Nevi Syndrome (CLOVES) 

For more information call or email Megan Metcalf at 513-803-2606 [email protected]

Kahle Lab AVM Research

The genetics of AVMs are poorly understood, and many theories currently exist with regards to their development, including the hypothesis that their development begins early in gestation. Kahle Lab is actively recruiting patients with brain or spinal cord AVMs and their families. Participants must have a formal diagnosis based on imaging.   This study is currently open to people in the United States.

If you are interested in participating, please email [email protected] with the following information:

  1. Mailing Address or Addresses where the swabs and paperwork will be sent
  2. Active contact telephone number
  3. Full Names and Ages of participants at each address that will provide DNA samples in your household
  4. Previously referred to genetics? If so, findings? 

First in Human Trial of Topical VT30 in Patients with Venous/Lymphatic Malformations associated with PIK3CA or TEK gene mutations – Venthera    

8/28/20 – VT30-101 is a 2-part first-in-human trial of topically administered VT30 to subjects with cutaneous venous malformations, lymphatic malformations, or mixed venolymphatic malformations associated with PIK3CA or TEK mutations.

Part 1 is a 4-week treatment, open-label, 4-sequence, escalating repeat-application cohort study, with intra-subject and inter-cohort dose escalation.

Part 2 is a 12-week treatment, randomized, placebo-controlled, double-blind, safety and exploratory efficacy study. Part 2 will be initiated only after the successful completion of Part 1 with results that demonstrate the general safety and tolerability of topically applied VT30. Up to 12 subjects who complete Part 1 may be enrolled into Part 2 of the study.

The primary objective is to evaluate the safety and tolerability of VT30. The study will also determine the dose and regimen of VT30 to be carried into Part 2 of the protocol. Other aims include documenting plasma drug levels of VT30 and VT10 and, on an exploratory basis, examining pharmacologic target engagement and change in potential efficacy readouts.

Compassionate Use Access of PIQRAY (formerly BYL719/alpelisib) [7-9-19]
The Novartis Managed Access Program (MAP) for PIQRAY use in PROS is available to patients in the US where PIQRAY is available for commercial use (as well as other countries where not approved).

The FDA approved PIQRAY for HR+/HER2- advanced breast cancer, and thus PROS patients may seek access to the medication through MAP.

Patients should contact their treating physicians who can, if clinically appropriate, make a request to Novartis for access to treatment using this link on the Novartis website

Opportunity for CLOVES Research (ongoing)

April 23, 2013 – Research Opportunity with National Institutes of Health (NIH)



CLOVES syndrome is different than most other genetic conditions in that it is not inherited.  The gene changes that cause CLOVES syndrome in a person are not found in that person’s parents, siblings, or children. CLOVES syndrome is caused by changes (“mutations”) in a gene called PIK3CA and these changes are only present in some of a person’s cells.  Just like people with CLOVES syndrome have some affected parts of their bodies and some unaffected parts of their bodies (for example, differences in just one leg but not the other, or skin changes in some places and not others), the PIK3CA mutations that cause CLOVES syndrome in a person are not present in all of that person’s cells. Scientists use different words to describe this, including “mosaicism,” and “segmental.” No matter what term is used, the important thing to know about CLOVES syndrome is that where and how you look for a causative mutation really matters. This graphic describes the genetics of CLOVES syndrome.

Genetic testing can be very helpful for people with CLOVES syndrome. Having a genetic test can help families and doctors understand treatment options that are already available.  Treatments that are currently being tested or may become available in the future may also rely on a person’s genetic test results. Many healthcare providers are still unfamiliar with what mutations to test for and what samples are needed. Approximately half of the families involved in the CLOVES syndrome community have told us they had difficulty with genetic testing. The most common challenges are insurance coverage and getting the right kind of genetic test.

Genetic testing for CLOVES syndrome/PROS is more complicated than other kinds of genetic testing. It is important to be sure that the right sample is sent for testing and to understand how different genetic testing laboratories perform the test.  You can read more about this in our FAQThis site also has a good explanation of genetic testing.

What sample will be used for testing?

Almost all traditional genetic testing is done using blood or saliva samples.  These are NOT the best samples to use for genetic testing for CLOVES syndrome.  PIK3CA mutations that cause CLOVES syndrome just can’t be detected as well (or at all) in DNA that comes from these types of samples. No genetic test is perfect, but if a mutation is there, choosing a sample that comes from a part of the body that is clearly “affected” (showing signs of CLOVES syndrome) has the highest chance of finding it. For most people, this means having a skin biopsy done.  Another option is to use tissue that might be available from a surgery that would ordinarily be thrown away. Having a skin biopsy (or sending surgical samples for genetic testing) takes more work for families and clinicians, and many parents don’t like the idea of having their child have a biopsy. Because genetic testing can be expensive and difficult to arrange, it’s often worth it to make sure that the best possible sample is used.

What laboratory will do the test?

Not all genetic testing laboratories (and there are LOTS of genetic testing labs!) test for CLOVES syndrome.  Most offer CLOVES syndrome genetic testing as part of a “panel.” Many different genes that may cause similar conditions are tested at the same time. In some cases, the lab will only test specific mutations within the PIK3CA gene. Sometimes a person’s insurance will cover genetic testing at some laboratories and not others. It’s important for you and your doctor to understand the specific test that will be done. Exome sequencing, a very comprehensive and increasingly common test, especially for people with rare conditions, may not be the best test for people with CLOVES syndrome. It is very expensive and is often only done using a blood sample. Many families tell us that they had exome sequencing as their first diagnostic test.   While CLOVES Syndrome Community does not endorse any of the following laboratories, they each offer tests that, when performed on the right DNA source or tissue sample, have a higher chance of finding a PIK3CA gene change compared to others.

University of Pennsylvania

Washington University

Boston Children’s Hospital

When considering genetic testing, here are some “green lights” and “red flags” that can help you and your doctor decide on the best test for you/your child:

Test Green lights – signs of a more appropriate test for CLOVES syndromeRed flags – signs of a less appropriate test for CLOVES syndrome
Sample typefresh tissue, frozen tissue, DNA extracted from tissueblood, saliva, DNA extracted from blood or saliva
Name of test“Somatic overgrowth panel” includes “CLOVES syndrome” or “mosaic overgrowth” in name of testName of test seems to test for something else, e.g., “polydactyly panel”
Coverage“deep sequencing” “ultra deep sequencing” “100x” “250x”“20x coverage”
Detection language“limit is 1%” “limit is 5%”“variants present at <20% may not be reliably detected”

How will the test be done?

There are lots of different ways genetic tests can be done.  Finding the responsible mutation in a person with CLOVES syndrome is more of a “needle in a haystack” situation than many genetic tests because even in the “perfect” sample, the percentage of DNA with the mutation is lower than with other genetic conditions. Genetic tests designed to find the low-frequency mosaic mutations common in CLOVES syndrome are the best ones for people with CLOVES syndrome to get.  It can be important to understand what the test’s lowest frequency is. Can the test find a mutation that may only be present in 1% of the DNA from the sample? 5%? 25%? Also, some genetic tests just look for specific mutations in specific genes, while others read through (“sequence”) whole genes. Having this information in advance can help families and providers pick the best test for the situation.

What will the results mean?

 A “positive” result means that the test found a gene change or mutation in a gene that is known to be associated with CLOVES syndrome.  Most people with CLOVES syndrome who get positive test results will have changes in the PIK3CA gene. A “negative” result can be complicated in a condition like CLOVES syndrome for a couple of reasons:

1) No genetic test is 100% perfect

2) A mutation may be present but not at a high enough level for the test to find. The lab may label any mutations found in less than 5% of the DNA in the sample as “negative.”

3) A mutation may not be present because the sample came from blood or saliva.  This is common in CLOVES syndrome and why we suggest that DNA from biopsies is the best sample to send for genetic testing

4) A “true negative:” we do not know 100% of the genes that cause CLOVES syndrome so even a perfect test from a perfect sample will not give a positive result in a person whose mutation in a gene that has not been discovered yet.

Additional Resources for Genetics:

Visual created by the National Institutes of Health to help explain PIK3ca mutations and overgrowth. [March 20, 2017] 

NIH Ongoing Research for PIK3CA mutations:
The National Institutes of Health does research testing of patients with all kinds of overgrowth. If you’d like to learn more, contact them at [email protected] or by phone at 301-435-6689. More information can be found here

CLOVES Genetic Mutation Discovery (5/31/12)
Researchers at Boston Children’s Hospital identify a genetic cause for CLOVES

Clinical Signs


CLOVES Syndrome is an overgrowth syndrome with complex vascular anomalies. CLOVES stands for Congenital, Lipomatous Overgrowth, Vascular malformations, Epidermal nevi and Scoliosis/Skeletal/Spinal anomalies. The syndrome was described independently by Saap et al. and Alomari [1,2]. The syndrome shows no inheritance among families of affected patients.

CLOVES syndrome is rare and very variable; ranging from mild to severe. The common features in most patients allow for proper diagnosis and distinction from other syndromes. The most consistent features of the syndrome are:

  1. Fatty Truncal Mass: Typically, a soft fatty mass of variable size is noted at birth. The mass can be seen in one or both sides of the back and abdominal wall and extending into gluteal or groin regions. The skin over the mass is covered with a red-pinkish birthmark known as a port-wine stain or capillary malformation. The fatty mass may extend into the chest, abdomen or into the spinal canal (around the spinal cord).
  2. Vascular Anomalies: In addition to the skin birthmark, patients with CLOVES syndrome have abnormal lymphatic and venous channels. In addition, a group of patients suffer from a more aggressive vascular anomaly (Arteriovenous malformation – AVM) around the area of the spinal cord.
  3. Abnormal extremities (arms and legs) and scoliosis (curving of the spine) are common. A person with CLOVES may have large wide hands or feet, large fingers or toes, wide space between digits and uneven size of extremities.
  4. Skin abnormalities include birthmarks, prominent veins, lymphatic vesicles, moles and epidermal nevus (light brownish slightly raised skin in the upper chest, neck or face).
  5. Other abnormalities include small or absent kidney, abnormal patella (knee cap), knee and hip joints.

Most people with CLOVES syndrome do not have all these signs, but rather a combination of abnormalities; though some can be subtle or deeply seated and requires a dedicated physical exam and proper imaging studies.

The diagnosis can be established right after birth, though prenatal diagnosis with modern imaging tools may be feasible [3].


Historically CLOVES Syndrome diagnosis has been made by medical exam, observed physical characteristics and clinical information/history. With the discovery of genetic mutation in CLOVES and PROS conditions, tissue testing for PIK3CA can be performed. The diagnosis can be established right after birth, though prenatal diagnosis with modern imaging tools may be feasible.


  • Fatty Truncal Mass
  • Vascular Anomalies
  • Abnormal extremities
  • Skin abnormalities
  • Other abnormalities include small or absent kidney, abnormal, knee and hip joints, and/or scoliosis.

The management of CLOVES syndrome can be very challenging and requires an interdisciplinary team of physicians with experience in overgrowth and vascular anomalies.


  1. Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowry RB, Biesecker LG. 2007. Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients. AmJ Med Genet Part A 143A: 2944-2958.
  2. Alomari AI. 2009. Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: A descriptive study of 18 cases of CLOVES syndrome. Clin Dysmorphol;18:1-7.
  3. Fernandez-Pineda I, Fajardo M, Chaudry G, Alomari AI. Perinatal clinical and imaging features of CLOVES syndrome. Pediatr Radiol.


Join the PIK3CA Related Conditions Research Roundtable:

As part of the development of the Patient-Led Collaborative Research Network for PIK3CA Related Conditions (PROS), CLOVES Syndrome Community is launching a new opportunity and space for researchers to connect, share and learn from one another.

Our Research Roundtable will meet every other month and will focus on knowledge exchange, feedback on ongoing projects, sharing work and research in progress.  The Research Roundtable will be moderated by Ralitsa Madsen (Sir Henry Wellcome Fellow, UCL Cancer Institute, UK). Each meeting will feature one 20-minute presentation, with time for questions and discussion, for a total of one hour.

This roundtable is for:

  • Basic and pre-clinical researchers in academia and industry 
  • Graduate students
  • CLOVES Syndrome Community funded research grantees
  • Patient advocacy organization leaders

Goals of the roundtable: 

  • To accelerate progress in basic PROS research through open knowledge exchange
  • To enable PROS researchers to share positive as well as null results independent of formal publication venues
  • To enable PROS researchers to get feedback on ongoing or planned projects, akin to an international “lab meeting” 
  • To foster international collaboration among PROS researchers

Why you should join:

  • Support patient-led collaborations for ultra-rare diseases
  • Because people with rare diseases matter 
  • Support Open Science
  • Benefit from expert feedback 

Expectations of group members:

  • Active participation (80% attendance)
  • Commitment to minimum one presentation a year
  • Commitment to share ongoing work independent of publication 
  • This is a closed-door conversation. All information shared within this meeting is considered confidential unless otherwise specified.

You must register for the roundtable here

2023 Research Roundtable Dates

(11am EST/ 4pm UK)

Thursday November 30, 2023 

2024 Research Roundtable Dates

(11am EST/ 4pm UK)

Thursday January 25, 2024

Thursday March 28, 2024

Thursday May 30, 2024

Thursday July 25, 2024

Thursday September 26, 2024

Thursday December 5, 2024

Upcoming Presenters :

January 2024 – Dr. Eulalia Baselga, SJD Barcelona Children’s Hospital, “Capillary malformation with overgrowth: Genotype/phenotype correlation”

March 2024 – cancelled

Past Roundtable Presenters

Dr. Benoit Bilanges, UCL Cancer Institute
“A small molecule activator of PI3Kalpha, a new tool to probe PI3K signalling and biology”

Sandra Castillo, Carreras Research “PIK3CA-driven vascular malformations”

Sarah Sheppard, NIH – “PIK3CA is the most common cause of vascular malformations in a cohort of 356 participants”

Dr. Wen Yi Aw, PhD – UNC Chapel Hill – “Microphysiological modeling of PIK3CA-driven vascular malformations”

Colin Ratcliffe, PhD – The Francis Crick Institute – “Imaging response to Akt kinase inhibition in 3D models”

Elisa Boscolo, Boscolo Lab and Dr. Adrienne Hammill, MD PhD – Cincinnati Children’s Hospital

Dr. Romuald Girard -“PIK3CA gain of function, a new insight in cerebral cavernous malformation pathogenesis”.

Ralitsa Madsen – Establishing MADR-based cell models for systems biology studies of PIK3CA activation

Emily Erickson , Toker Lab  – Targeting the PI3K/AKT pathway using pan-AKT degraders

Ana Angulo-Urarte – PIK3CA Variants in PROS

Working with Industry


CLOVES Syndrome Community seeks the highest level of ethical conduct in engagement with biopharmaceutical companies. The goal of engaging with biopharmaceutical companies is to help enable the development of therapies while maintaining our autonomy.

Guidelines for Interactions Between CLOVES Syndrome Community and Biopharmaceutical Companies


The interactions between CLOVES Syndrome Community (“CSC”) and biopharmaceutical companies are important and complex. Collaborations between these two stakeholders have become more common in recent years as CLOVES Syndrome Community has evolved and biopharmaceutical industry activity has increased, particularly in rare diseases.

The principles outlined in the following guidelines are intended to help CLOVES Syndrome Community navigate critically important interactions with biopharmaceutical companies.

These guidelines were developed with input from an Independent Expert Panel from the rare disease community with expertise in these collaborations from both the industry and patient advocacy organization point of view. More information on the Independent Expert Panel and the process for developing these Guidelines is provided in the article entitled “Principles for interactions with biopharmaceutical companies: the development of guidelines for patient advocacy organizations in the field of rare diseases,” published in The Orphanet Journal of Rare Diseases, 2018.


CLOVES Syndrome Community seeks the highest level of ethical conduct in engagement with biopharmaceutical companies. The goal of engaging with biopharmaceutical companies is to help enable the development of therapies while maintaining our autonomy. All interactions between CLOVES Syndrome Community, industry and the disease community should be transparent; should enable trust, accountability and shared learning; and ultimately should work most efficiently and effectively toward advancing meaningful treatments for patients.

There are four main areas of engagement between CLOVES Syndrome Community and biopharmaceutical companies described in the following Guidelines:

  1. Identification and Engagement with Companies
  2. Patient Engagement and Patient Privacy
  3. Financial Contributions
  4. Clinical Trial Communication and Support

Patient Support & Emotional Wellbeing


Patient-centered care is key to obtaining positive health outcomes. Studies have shown it is vital to treat the whole patient and not just the disorder. We strongly suggest you refer all families affected by CLOVES to our site. Here they can learn more about CLOVES, join our registry, obtain information on a number of resources, and find support by joining our community.



The publications database will serve as a reference list and educational resource for our existing community as well as young researchers and clinicians as we develop our International PIK3CA Conditions Collaborative Research Network. The database contains information as well as Pubmed links to all published literature on CLOVES and more broadly, on PROS. In this resource, we highlight different article types such as primary research, case series, and reviews, as well as areas of research such as diagnosis, management, and treatment of CLOVES/PROS. New articles will be added each month as they are published to keep our community up to date. 

The publications database is best viewed on a large screen such as a computer or Ipad.

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“Never doubt that a small group of thoughtful, committed citizens can change the world; indeed, it’s the only thing that ever has.”
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