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This month's The Genomic Landscapediscusses recent studies that reveal knowledge gaps in the understanding of how the genome varies from person to person and population to population; a new educational genomics toolkit for physicians; electronic medical records and genomics; and NHGRI's Dr. Leslie Biesecker's election as the 2019 president for ASHG.
This month's The Genomic Landscape marks the 40th anniversary of the beginning of DNA sequencing methods. Developed by Fred Sanger and Alan Coulson, and Allan Maxam and Walter Gilbert, these methods eventually helped spawn the field of genomics. Dr. Green also sends best wishes to departing NHGRI researcher Barb Biesecker, highlights a recent dog genome project Reddit AMA and provides a reminder to learn your family health history on Thanksgiving.
This month's The Genomics Landscape features stories about The GTEx Project's legacy, which lives on in its now publicly available atlas for studying human genomic variation and how it relates to gene expression. Also, best wishes to Dr. Jean McEwen, who recently retired from NHGRI's Division of Genomics and Society and management of the Ethical, Legal, and Social Implications (or ELSI) Research Program; a request for comments on the Genomic Data Sharing Policy; and changes to policies that guide the stewardship of NIH-funded clinical trials.
With the acceleration of interest in genome editing, NHGRI Director Eric Green addresses the topic in this month's The Genomic Landscape, taking a comprehensive look at genome editing technology, NHGRI's use of a variety of gene editing techniques and a new resource about genome editing available on genome.gov. Other topics include genomics and clinical care, NHGRI's summer interns and a visit from Native graduate health fellows to the NIH Clinical Center and NHGRI.
In June, nearly 300 people attended a three-day Congress on the Ethical, Legal, and Social Implications (ELSI) of genomics research. The fourth such meeting, entitled Genomics and Society: Expanding the ELSI Universe, was funded by NHGRI through a grant to Columbia University Medical Center, and held on the campus of UConn Health and The Jackson Laboratory for Genomic Medicine in Farmington, CT.
The various Institutes and Centers at NIH differ in their use of the available approaches for funding extramural grants. Some mostly fund 'classic' investigator-initiated applications, in which the proposed research is almost entirely formulated and executed by the investigator(s). Others make greater use of approaches for funding more managed research projects that often involve the formation of consortia that conduct research with a more 'team science' style.
As genomics becomes increasingly present and relevant in both the public sphere and medical care, there is a clear need to enhance genomic awareness and understanding. Yet, genomic literacy has, in general, not kept pace with genomic advances, and filling this gap is becoming urgent. In partnership with the Foundation for the National Institutes of Health, NHGRI co-hosted a strategic visioning meeting in March that contemplated the possible establishment and launching of a Genomic Literacy, Education, and Engagement (GLEE) Initiative. GLEE is envisioned as a national campaign to enhance genomic literacy and to close the above-mentioned gap. The meeting was attended by ~160 people from diverse communities, including academia, industry, community-based organizations, non-profits, government, and K-16 education organizations.
Early this month, genomic medicine researchers, clinicians, and other experts will gather in Silver Spring, Maryland as part of the latest edition in a series of meetings centered around the challenges of bringing genomic medicine into routine clinical practice (see the meeting webcast here live on May 2 and 3). The ten 'Genomic Medicine meetings' held to date are one example of the productive work of the NHGRI Genomic Medicine Working Group (GMWG), a designated working group of the National Advisory Council for Human Genome Research.
NHGRI has long promoted the widespread sharing of genomic data and the creation of robust resources to facilitate the organization, management, and access to those data. We have supported many databases over the years, and have participated in efforts to develop strategies that foster data science as biology moves toward an era of "big data." Emerging from these and analogous efforts in other disciplines have been 'core data resources' that are fundamental to research in the life sciences. These data resources are used and relied on by scientists around the world.
Every year in late February, there is a date designated as Rare Disease Day. The goal of this annual event is to raise awareness about rare diseases and the lives they impact. Just last week, NIH held its annual symposium for Rare Disease Day; the archived webcast is accessible here. A rare disease is defined as a disorder or condition affecting fewer than 200,000 people in the United States. However, as it is often said, rare diseases considered together are not so rare! Over 7,000 rare diseases have been identified, with upwards of 25 million people affected by rare diseases in the United States alone- similar to the number of people affected by diabetes.
The completion of the Human Genome Project and subsequent genomics research over the last ~14 years have reinforced the notion that humans across the globe are more alike than they are different. But we also know that many factors - ancestry, environment, and social factors - have a profound effect on human health. One challenge facing genomics and biomedical research is how best to describe the diversity of the human population as part of research studies.
On December 31, NHGRI said goodbye to its founding Director of the Division of Genome Sciences in the Extramural Research Program, Dr. Jeffery Schloss. After a truly remarkable career that included leading NHGRI's DNA sequencing technology development program, Jeff is embarking on a well-deserved journey into retirement.
Reflecting on the recent Thanksgiving holiday, I wanted to remind you about the My Family Health Portrait tool, which offers families a place to share health information and learn about familial health conditions. What better time to do so than during the holiday season when extended families often gather? To learn more about family health history, see NHGRI's recently released infographic as well as a joint feature on the topic with the Centers for Disease Control and Prevention (CDC).
I do not know about the rest of you, but my most frequent thought for the past couple of months has been "are we there yet?" There seem to be so many things in play right now, including the election, the need to pass a Fiscal Year 2017 federal budget, and the inevitable transition to a new administration. The good news is that we are (hopefully) almost there on all of these fronts. Despite these uncertainties, the pace of genomic advance does not seem to be slowing down, as evidenced by the myriad impressive things that I saw firsthand reported at last month's American Society of Human Genetics meeting in Vancouver.
I frequently boast of the accomplishments of the NHGRI Advanced Sequencing Technology Program, often referred to as the $1000 Genome Program. In fact, I am on record as saying that - in my opinion - it is the most successful technology development program in NIH history. As an example, such glowing accolades were heard out of my mouth a couple of weeks ago at the 78th meeting of the National Advisory Council on Human Genome Research. Simply stated, the $1000 Genome Program has been spectacularly catalytic in advancing the development and refinement of new genome sequencing technologies. The fruits of multiple rounds of grant awards aimed at stimulating technology development in this area have helped to create the various new 'next-generation' DNA sequencing platforms that are now available.
Starting at the inception of the Human Genome Project, NHGRI has been at the forefront of research into the Ethical, Legal, and Social Implications (ELSI) of genomic advances. From stand-alone investigator-initiated studies to research embedded within large international genomics collaborations (e.g., HapMap Project, 1000 Genomes Project, and H3Africa), NHGRI has funded in-depth research endeavors that aim to ask and answer questions about individuals' and communities' attitudes about genomics, legal issues associated with genomics, the responsibilities of genomic researchers to their research participants, and numerous other issues. This funding support has gone to investigators from a wide range of disciplines -bioethics, law, behavioral and social sciences, policy, philosophy, and theology.
To explore the complexity of the human genome and its involvement in human disease, genomicists approach research questions from many angles. In an effort to advance genomic medicine research, NHGRI continually explores ways to use genomic-based clinical tools from the "bedside" and basic tools from the "bench." In April, NHGRI's Genomic Medicine Working Group held its 9th Genomic Medicine Meeting (GM9), entitled "Bedside to Bench - Mind the Gaps." GM9 aimed to continue our long-term effort to address the many challenges of bringing genomics to medicine. GM9 explored how to engage basic genome scientists to tackle the many applied research questions in genomic medicine.
With the human genome consisting of billions of chemical units, scientists have a tremendous amount of information to sift through to understand how the genome works and how it influences human health and disease. Oftentimes, scientists encounter a genomic variant (i.e., an altered spelling) in a gene that they suspect might play a role in a disease being studied. But how do they prove such a relationship? Establishing such 'proof' can be quite challenging. But additional experimentation using model organisms can often provide a key piece of the puzzle.
Often, the advances made in technologies for genome sequencing are cited as a pivotal achievement that will change medical practice in important and productive ways. In fact, I am often a person making such claims, and I stand by them. But that is not to say that I think the path forward will be easy - rather, there are many issues that need to be explored in bringing genome sequencing into medicine. NHGRI has a number of major research programs investigating those issues, a key one being the Clinical Sequencing Exploratory Research (CSER; pronounced 'caesar') Program.
Scientific collaboration on a large scale has been a hallmark of genomics since the beginning of the field. NHGRI has been fortunate to be at the center of many large collaborative projects, such as the Human Genome Project (HGP). While the HGP represents one incredible milestone in the path to understanding human biology, it also resulted in new technologies and resources that are now foundational for many areas of biological research. This progression is nicely illustrated by an NIH-wide collaboration that has given researchers access to key genomic resources for the past 20 years - the Center for Inherited Disease Research (CIDR).
NHGRI's Intramural Research Program houses unique investigative endeavors of various types. One such enterprise is the Immersive Virtual Environment Test Unit, which encompasses the Immersive Virtual Testing Area (IVETA). Founded in 2006, IVETA is an experimental behavioral science research laboratory within the NIH Clinical Center that serves the NHGRI Social and Behavioral Research Branch (SBRB). The focus of IVETA is the development of advanced communications methodologies and technologies for use in behavioral research.
Since 2003, NHGRI has celebrated 'National DNA Day' on April 25 to commemorate the successful completion of the Human Genome Project and the discovery of DNA's double-helical structure published on this date in 1953. This annual celebration offers students, teachers and the public many exciting opportunities to learn about the latest advances in genomics and to explore how those advances might affect their lives. National DNA Day is a favorite of mine, in part because it gives NHGRI staff the chance to engage with the community through a range of activities - from classroom events to web-based forums.
A few weeks ago, NHGRI renewed its Genome Sequencing Program (GSP), the Institute's largest single grant program that has its origins in the Human Genome Project. Since NHGRI grants are always awarded for a limited number of years at a time, the GSP has experienced a number of 'renewals' - and so this renewal could mistakenly seem like a simple and mindless process. But rest assured, this was not the case!
The billions of chemical units of DNA that make up a human genome work in often mysterious ways in providing the instructions to build and operate all the cells in the human body. The Human Genome Project, which determined the order of those chemical units (also called nucleotides or bases), was completed nearly 13 years ago. So, what is left to understand? As it turns out - a ton! In fact, genome scientists are just beginning to scratch the surface of understanding all the intricacies of human genome function and how genomic differences influence health and disease.
In September, NHGRI convened a roundtable meeting to discuss the opportunities and challenges associated with the inclusion and engagement of underrepresented populations in genomics research. The roundtable was organized by NHGRI Senior Advisor on Genomics and Health Disparities, Vence Bonham, J.D. Mr. Bonham's role as Senior Advisor dovetails with his research in the Health Disparities Unit, part of the NHGRI Social and Behavioral Research Branch, in which he conducts research at the intersection of public policy, healthcare inequities, and genomics.
This month, we celebrate National Family History Day. On Thanksgiving, the U.S. Surgeon General encourages you to talk with your family about your family health history. The "My Family Health Portrait" online tool can help you organize your family health history. You can even print out the compiled information to share with family members and your doctor(s). I hope you will take a moment to talk with your family about this important topic - this month or any time of the year. In this month's The Genomics Landscape, I highlight the 1000 Genomes Project, which came to a close last month. See various details below, along with other information items that I hope will be of interest to you.
November Genomics Landscape
This month brought a historic 'odometer moment' for the field of genomics - October 1, 2015, marked the 25th anniversary of the launch of the Human Genome Project. I, for one, cannot believe a quarter-century has now passed since many of us started working on the project. At the same time, it is truly incredible to think about how far genomics has progressed since that time. I thought the significance of this anniversary warranted making this topic the lead story in this month's The Genomics Landscape; in addition, I reflect on this important anniversary in a recent video interview now available on the NHGRI website.
October Genomics Landscape
Throughout its history, NHGRI has been committed to sharing details of its organization and scientific programs with the scientific community and the general public. The Institute has typically communicated its scientific vision through more detailed 'strategic plans' - crafted in collaboration with the research community and published in the scientific literature. These strategic plans have been largely crafted for a scientific audience. To reach a broader audience, the Institute recently developed a new 'eye-catching' NHGRI Brochure. The brochure provides various information about NHGRI as an organization - our history, our core values, our compelling research portfolio, and our various other programs - in a format targeted for a broad audience.
September Genomics Landscape
In November 2011, NHGRI and the National Heart, Lung, and Blood Institute (NHLBI) established the Centers for Mendelian Genomics (CMG) program, the goal of which is to identify genomic mutations underlying Mendelian diseases using modern genome-sequencing technologies and to develop the most effective research approaches for uncovering the genetic basis of Mendelian diseases. Mendelian diseases, named after Gregor Mendel (the founder of modern genetics), are rare diseases that are typically transmitted from parents to offspring. While 'rare' at the individual level, Mendelian diseases are thought to collectively affect 25 million people in the United States.
August Genomics Landscape
Since 1996, NHGRI, in partnership with Johns Hopkins University (JHU), has offered a unique program: The JHU/NHGRI Genetic Counseling Training Program (GCTP). The program focuses on education in cutting-edge genomics, in-depth psychological counseling training, and research skills for thesis development and execution. The GCTP aims to produce the next generation of leaders in the field. Graduates earn their degree from the Johns Hopkins Bloomberg School of Public Health.
Some day in the not-too-distant future, many people will have their genomes sequenced as part of their routine medical care. It is the hope of many that such genomic information will lead to improved approaches for preventative medicine and personalized treatments. To realize such a future, a detailed knowledge of the role that individual DNA variants play in genome function is needed. An exciting research endeavor that aims to generate that knowledge is the Genotype-Tissue Expression (GTEx) Project.
The recently announced Precision Medicine Initiative is on the minds of many people these days. Numerous developments are unfolding as the planning phase proceeds, and it seems that everywhere that I go, scientists and non-scientists alike are eager to hear details. Accordingly, I have added a new 'spotlight' on the Precision Medicine Initiative within The Genomics Landscape - immediately before the section containing links of interest. Each month, this spotlight will feature news regarding the Precision Medicine Initiative, so stay on the lookout for these regular updates.
On April 24, we will celebrate National DNA Day 2015, which commemorates the completion of the Human Genome Project in 2003 and the discovery of DNA's double-helical structure in 1953. DNA Day offers students, teachers, and the public exciting opportunities to learn about the latest advances in genomics and to explore how genomics may be meaningful to their lives. Each year, NHGRI celebrates DNA Day with a number of events. This year, the Institute is working to engage teachers in genomics education through a variety of activities and new teaching resources. Below, I highlight some of our DNA Day 2015 activities, as well as our teacher-focused resources that bring genomics into the classroom.
Roughly 100,000 years ago, humans migrated out of Africa and started to populate the globe. Although the human species is now associated with significant phenotypic variation, all humans have a genetic origin in Africa. The genomes of people currently living in Africa are more varied than those of people living anywhere else on Earth. Studying the genomes of Africans thus offers important opportunities to characterize and understand genomic variation. Despite this, Africans are largely underrepresented as both research participants and scientists in genetics and genomics.
February's The Genomics Landscape is later than usual for a good reason! I was in the White House East Room with a number of other NHGRI and NIH colleagues to hear President Obama announce the Precision Medicine Initiative. I'm honored to be part of the extensive planning leading to last week's unveiling, and it will be gratifying to have NHGRI involved in making this important initiative a reality.
February Genomics Landscape
Large-scale genome sequencing has been a central component of NHGRI's Extramural Research Program since the NHGRI's inception, starting with the Human Genome Project. In this month's The Genomics Landscape, I describe the next phase of NHGRI's Genome Sequencing Program and highlight additional items that I hope will be of interest to you.
January Genomics Landscape
It is hard to believe (and, in fact, I find it shocking!) that today marks the beginning of my 6th year as Director of the National Human Genome Research Institute. The last five years have gone by in a flash, and I feel quite proud about what we have accomplished.
December Genomics Landscape
This issue of The Genomics Landscape describes the evolution of genome sequencing and its impact on public health surveillance and infectious disease diagnostics. Also highlighted: The first BD2K awards, National Family History Day, a new NHGRI executive officer and how to comment on our recent genome sequencing workshop.
November Genomics Landscape
In this month's The Genomics Landscape, Dr. Green describes a recent release from the U.S. Food and Drug Administration (FDA) announcing the steps that they are taking to help ensure the reliability of certain diagnostic tests. The FDA announcement comes at a critical transition for genomic medicine.
October Genomics Landscape
Rapid and broad data sharing has been a hallmark of genomics since the early days of the Human Genome Project (HGP). Today, it is well-appreciated in genomics that the work of individual investigators and large collaborative efforts alike benefits from access to data resources such as ENCODE, 1000 Genomes, and The Cancer Genome Atlas (TCGA). Furthermore, the cumulative benefit realized through the culture of genomic data sharing transcends individual projects, and has been essential to accelerating genomics research across the board.
September Genomics Landscape
The Undiagnosed Diseases Program (UDP) launched in 2008 as a partnership among NHGRI, the NIH Clinical Center and the Office of Rare Diseases Research, seeks to provide answers to patients with mysterious conditions that have eluded diagnosis. This multidisciplinary clinical and research team has diagnosed ~100 patients, discovered two previously unknown diseases and identified 50 genes not previously associated with any other human disease.
August Genomics Landscape
A big change has occurred at NHGRI this summer. Founding staff member, Dr. Mark Guyer, formally retired from federal service on June 30. For most of his time at NHGRI, Mark was a key leader of the Extramural Research Program; most recently, he was the NHGRI Deputy Director. Much could be said of Mark's career in the federal government. For example, I could describe his critical role in the Human Genome Project, or name the many genomics programs that he has helped to establish and nurture, or tell you about the vital role he has played as a trusted advisor to me and other NHGRI leadership. Instead, I will use this opportunity to share some thoughts about Mark from other people that he has worked with over the course of his impressive career.
July Genomics Landscape
Starting with NHGRI's original raison d'être - the Human Genome Project - NHGRI has been closely tied to or led a number of very high-profile genomics projects. These efforts have produced massive volumes of documents, notes, emails, slides, photographs, videos and other materials. As the institute's scientific portfolio widens, the pace of generating such materials is only growing. Several years ago, I realized that we were at risk of losing valuable materials that are of historic value because we lacked a systematic approach for archiving institute resources.
June Genomics Landscape
The fast-paced nature of genomics provides seemingly endless opportunities to pursue exciting research. While invigorating, this presents challenges when it comes to ensuring the presence of a strong pool of future researchers and providing genomics expertise to individuals at different points in their scientific careers. Providing genomics training is thus an important component of NHGRI's mission. How does NHGRI's Extramural Research Program prioritize its training efforts? How do we ensure that the appropriate expertise is available to the researchers who will solve complex genomic problems and bring genomics to medical care?
May Genomics Landscape
Engaging students at a young age offers our best chance to inspire them about scientific concepts and the process of scientific inquiry. For that reason, NHGRI has an active and robust outreach and education program. On April 25th, we will celebrate the 12th Annual National DNA Day, which commemorates the completion of the Human Genome Project in 2003 and the discovery of DNA's double-helical structure in 1953. NHGRI celebrates DNA Day every year with a number of events. Below, I highlight some of our DNA Day programs, as well as our other student- and teacher-focused activities that bring genomics into the classroom.
April Genomics Landscape
The most important task for an Institute's Extramural Research Program (ERP) is to develop and support a high-quality research portfolio. To this end, NHGRI has undertaken multiple strategic planning efforts, starting with the Human Genome Project and most recently culminating in the publication of "Charting a course for genomic medicine from base pairs to bedside" in 2011. While determining the broad goals for genomics is key for our research agenda, more challenging is making hard decisions about the relative priorities for the various programs that we could fund. Add to that the current challenging budget situation, and we quickly find ourselves facing many difficult choices.
March Genomics Landscape
The topic of 'Big Data' (of all sorts) has become a hot one across the industrial, academic, and non-profit sectors. Recognizing the importance of biomedical Big Data to NIH, a Data and Informatics Working Group of the Advisory Committee to the NIH Director made a set of recommendations in 2012 that outlined programmatic ways for NIH to address the opportunities and challenges facing all biomedical researchers in accessing, managing, analyzing, and integrating the increasingly large amount of data. On the basis of that report, the Big Data to Knowledge (BD2K) Initiative was conceived.
February Genomics Landscape
As mentioned in last month's The Genomics Landscape, the NHGRI Intramural Research Program (IRP) recently reached its 20-year milestone. With its diverse spectrum of research- from genomic technology development to clinical genomics research and everything in between- the NHGRI IRP continues to serve as an important focal point for genomics research at NIH and worldwide. One of the IRP's key contributions to genomics research is the Social and Behavioral Research Branch (SBRB), now celebrating its 10th anniversary.
January Genomics Landscape
When NHGRI published its new strategic vision for genomics (Charting a course for genomic medicine from base pairs to bedside) in 2011, we recognized that the Institute had a lot to learn about the research needed to apply genomics to clinical care. At the same time, it seemed critical that we begin to establish a foundation of research programs that would facilitate the implementation of genomic medicine, so we decided to jump in and start swimming!
December Genomics Landscape
Following an extensive search process, I am delighted to announce my selection for the first Director of the newly established Division of Genomics and Society: Dr. Larry Brody. A long-standing member of the Institute, Larry is currently Chief of the Genome Technology Branch within our Intramural Research Program and Chief Scientific Officer of the trans-NIH Center for Inherited Disease Research.
November Genomics Landscape
Today marks the beginning of the third week of Fiscal Year 2014 for the U.S. federal government. Originally, I intended to send out this message on October 1st, at the start of the Fiscal Year. But, among its many other effects, the 16-day government shutdown prevented that. Unfortunately, even though the government has reopened, it is going to take many weeks to resolve the numerous problems created by the shutdown. We are well-aware that the shutdown not only affected us as federal employees, but many of you as well, and those of us at NHGRI (and NIH) are working hard to normalize our operations.
October Genomics Landscape
On April 14, 2003, the National Human Genome Research Institute (NHGRI) and our international partners announced the completion of the Human Genome Project (HGP) and the successful generation of a highly accurate and publically available reference sequence of the human genome. Those ordered ~3 billion letters provided the most fundamental knowledge about the human genetic blueprint and gave us a framework of knowledge for pursuing numerous new and exciting genomic studies.
At its recent annual meeting, the Board of Directors of the American College of Medical Genetics and Genomics (ACMG) approved the first set of practice guidelines to help doctors begin to navigate this new area. These practice guidelines represent an important step in using genomic information for routine medical care, a key goal put forward in NHGRI's 2011 strategic plan for genomics.
NHGRI could be called the institute of big questions - and answering big questions often takes big efforts. The big question that led to the creation of the National Human Genome Research Institute (NHGRI) was: "What is the sequence of the human genome?" It was a hard question to contemplate in the mid-1980s, less than four decades after the structure of DNA had first been elucidated and at a time when DNA sequencing technologies were in their infancy. Answering the "3 billion letter" question seemed like a herculean task at the time.
Early in the summer of 2013, the Smithsonian's National Museum of Natureal History (NMNH) will open a special exhibition on genomics and the human genome. This opening is timed to commemorate the 10th anniversary of the completion of the Human Genome Project, which produced the first high-quality reference sequence of the human genome, and the 60th anniversary of the famous Nature paper in which James Watson and Francis Crick first reported DNA's double-helical structure.
For years, many considered the Human Genome Project to be biology's equivalent to "the moon shot." In collaboration with its global partners, the U.S. government did what no individual or company could do: invested in a technologically risky scientific enterprise with a potentially big payoff. The project was an overwhelming success, delivering the first rough draft human genome sequence in 2000 and the final high-quality version in 2003 - ahead of schedule and under budget.
This February, we celebrate the tenth anniversary of the initial sequence and analysis of the draft human genome sequence published in Nature with input from thousands of scientists working on behalf of the Human Genome Project. The analysis was a game changer. Before the genome, a researcher might spend months acquiring DNA and trying to identify a gene. After the genome, the researcher could open a web browser and look it up. The sequence and analysis of the human genome accelerated research dramatically.
Five-time, Oscar-nominated actress Glenn Close had hers done. So did Nobel Peace Prize winner Archbishop Desmond Tutu. The double helix-writing geneticist James Watson did not want to know about everything that was in his. But everyone wants to know what is in British heavy metal rocker Ozzy Osbourne's - it might help explain how he is still alive today after decades of dissolute living.
Ten years ago this June, my predecessor, Francis Collins, stood in the East Room of the White House with President Bill Clinton and declared the first draft of the human genome sequence complete. It's been a remarkable decade for the field of genomics, and this year, 2010, will be another important one.
This is a profoundly exciting time for the National Human Genome Research Institute (NHGRI) and for genomics. There are vast opportunities for genomics research to make major contributions to our understanding of human disease, including its diagnosis, treatment and even prevention. As I take the helm of NHGRI, I find the institute well-positioned to pursue its important mission by capitalizing on these opportunities.
Last Updated: December 5, 2017