Tag: biological threats

Event Summary: Building Capacities for Addressing Future Biological Threats

by dkellogg97, posted in Commentary

Defining Convergence

By Geoffrey Mattoon, Biodefense MS Student

On Tuesday, 20 September, the Council on Strategic Risks (CSR) hosted the “Building Capacities for Addressing Future Biological Threats” webinar, which included keynote speaker Dr. David Christian (Chris) Hassell, Deputy Assistant Secretary for Preparedness and Response at ASPR, speakers Dr. Pardis Sabeti, Professor at the Center for Systems Biology at Harvard University, and Dr. Akhila Kosaraju, CEO and President of Phare Bio, and was moderated by Dr. Yong-Bee Lim, Deputy Director of the Janne E. Nolan Center on Strategic Weapons and George Mason Biodefense Program alumni. Together they discussed the evolving biological threats landscape and the means that exist to improve preparedness and response. This event follows the previous webinar “The American Pandemic Preparedness Plan: One Year of Progress & The Path Forward,” also hosted by CSR on 8 September, and focused heavily on the need for greater cooperation, collaboration, and innovation to prepare for the next pandemic.

             Dr. Hassell began the event by highlighting the misconceptions associated with the terms “convergence” and “bioconvergence” within the field. His concern was that these terms have become buzzwords within biodefense and their use implies that the different fields and disciplines necessary for biodefense are converging or cooperating organically. Such a misconception leads those within and outside of the field to assume that unity of effort is common and effortless, which is not the case. Barriers to convergence are prevalent and numerous, both in government and private sectors. Dr. Hassell provided an example from his previous experience in the Department of Defense developing chemical detectors, comparing a lack of higher-level convergence to the lack of standardized interfaces on different detectors preventing operators from gaining competency on all systems after mastering any single system. Such stove-piping of systems and efforts prevents convergence and is common across biodefense. The solution is a greater degree of crosstalk between disciplines working towards a unified solution or goal. Providing another example of this failure of convergence, Dr. Hassell highlighted the recent Pentagon appropriations for biodefense failing to account for the need for cyber funding to be successful against future threats as that discipline becomes more critical.

            Dr. Hassell also indicated that biological threats, in addition to the biodefense, are converging. As biotechnology and other life sciences continue to advance, the line between chemical and biological threats blurs. Previous research has demonstrated this growing convergence, from opioid-producing yeast conducted by Galanie et al. published in Nature to chemical synthesis of toxins conducted by Matinkhoo et al. in the Journal of the American Chemical Society. He urges a greater convergence of chemical and biodefense disciplines to effectively overcome these threats in the future. Such efforts would come at a substantial cost and require the reorganization of numerous government agencies, but it may be necessary to respond to the evolving threat landscape and enable more efficient use of future funding to unify efforts.

            Dr. Hassell then commented on the need for greater inclusion of data sciences, data technologies, and nanotechnologies in future biodefense efforts. The necessity of greater convergence between chemical and biodefense and the inclusion of these disciplines is a key requirement identified in Biodefense in the Age of Synthetic Biology, a report prepared by the National Academies for the Department of Defense in 2018. The addition of these technology-based disciplines is indicative of a greater requirement for technology convergence in chemical and biodefense efforts to combat the rising technology integration in the threat landscape. Modern biotechnology has created significant risk of dual use to create ever greater biological threats. Dr. Hassell pointed to the recent “Dual Use of Artificial-Intelligence-Powered Drug Discovery,” published by Urbina et al. in Nature Machine Learning, that indicated how easy it may be for a machine learning system designed with the best of intentions to identify new therapeutic disease inhibitors to be reprogrammed to instead identify novel toxin molecules. In that report, the MegaSyn system was able to generate 40,000 novel VX molecules in less than 6 hours. Dr. Sonia Ben Ouagrham-Gormley, Associate Professor at George Mason University and author of Barriers to Bioweapons, indicated such results do not directly equate to actionable threats on the Radiolab episode 40,000 Recipes for Murder that covered this journal article, but they still are indicative of the evolving chemical and biological threat landscape. Dr. Hassell also indicated the convergence of other disciplines critical to future biological threats, including climate change, which is enabling greater zoonotic spillover events, generating new and often novel biological threats.

            Dr. Pardis Sabeti underscored deadly infectious diseases as an existential threat to humanity during her remarks. She agreed with Dr. Hassell’s call for greater convergence and stated we must aspire to use technology to outpace the evolution of diseases so that we can be more anticipatory and less reactionary in the face of future outbreaks. She emphasized that COVID-19, though a recent a traumatic pandemic, is not the biggest threat we have faced or could face in the future. She argued we are on the precipice of cataclysm if we do not relentlessly pursue these efforts of convergence to enhance biodefense. Infectious disease is an existential threat that we can address because the tools necessary for biodefense are not bespoke or esoteric. Effective current and future biodefense tools, she argued, must be broad spectrum, offer daily value, contain transferrable benefits and knowledge, and be embraced at a cultural level to be effective. In line with the previous CSR webinar on COVID-19, Dr. Sabeti called for a greater commitment to community engagement as a key effort to combat future biological threats.

            Dr. Akhila Kosaraju then emphasized the need to take novel technologies required for biodefense out of the lab and into the field. She also supported the need for greater convergence, stating such efforts must be intentional to be successful. Her company, Phare Bio, exemplifies such efforts, employing AI and deep learning to enable rapid antibiotic discovery to overcome rising drug resistances. This approach provides Phare Bio a strategy to overcome the drug development “valley of death” where most current pharmaceutical development fails and presents an opportunity for other organizations like it across biodefense.  Modern biodefense efforts must emphasize biotechnology, relying on computational biologists, bioengineers, and other technical experts to maximize advances in the field.  She also indicated a need for organizations like The Audacious Project, a backer of Phare Bio, to effectively unify disciplines to solve intractable problems like drug resistance. The Audacious Project is a “collaborative funding initiative catalyzing social impact on a grand scale” across a broad range of disciplines that seeks to de-risk and encourage innovation. Injection of philanthropic, grant, or even government funding sources to adequately de-risk the “valley of death” and other obstacles is essential to future preventative and treatment therapeutics. Additionally, biodefense must strive to recognize small players in the field that often offer bespoke technologies and solutions that can accelerate efforts beyond that of the usual bigger players, as demonstrated throughout the COVID-19 pandemic. Efforts like Operation Warp Speed serve as foundational examples to the benefits such efforts can provide to the future of biodefense.  

Pandora Report 10.7.2016

by spopescu, posted in Pandora Report

TGIF and cheers to another week of biodefense news! Check out the GAO multimedia video on the risks of incomplete inactivation of pathogens. A whistleblowing former Pasteur Institute official in South Korea is reporting that a scientist for the South Korean branch took MERS-CoV samples on a commercial flight from Seoul to Paris without proper clearance and violated UN rules and French laws. The CDC is reporting a spike in the number of acute flaccid myelitis (AFM) reported. This rare polio-like illness can cause paralysis and was linked to outbreaks of enterovirus D68 in 2014. Ever wondered about opportunities to finance pandemic preparedness? Bill Nye has a new video on the “science illiteracy” of U.S. leaders, pointing to Ebola and climate change response as indicators of mistrust of science within the U.S.

Don’t Miss the Biological Threats in the 21st Century Book Launch!
screen-shot-2016-09-12-at-8-00-42-pmMake sure to RSVP by Sunday for the upcoming (October 14th)  book launch of Biological Threats in the 21st Century! Biological Threats in the 21st Century introduces readers to the politics, people, science and historical roots of contemporary biological threats through rigorous and accessible chapters written by leading scholars and supplemented by expert point-of-view contributions and interviews. The book launch will feature a panel discussion on the threat of biological weapons and the role of scientists in bioweapons non-proliferation and disarmament. The event is free and open to the public. Lunch will be available, first come, first serve, beginning at 11:45 AM so please RSVP. Attendants will also be able to pick up the book at a 15% discount.

GMU Biodefense Graduate Program Open Houses Biodefense_133x400
We invite you to attend an open house to learn more about the Schar School of Policy and Government. The session will provide an overview of our master’s degree programs, an introduction to our world-class faculty and research, and highlights of the many ways we position our students for success in the classroom and beyond. Our admissions and student services staff will be on hand to answer your questions. Check out the next MS info program on Wednesday, October 19: 6:30pm-8:30pm- Arlington Campus, Founders Hall, Room 126

Drawing on world-class original research and high-level practical experience, our faculty prepare students to be creative and effective participants in policy-making and political discourse.  By working closely with these faculty to conduct research that influences decisions at the local, national and international levels, our PhD graduates emerge prepared for high-powered careers in the public, private, and nonprofit sectors. The next PhD info session will be on Wednesday, October 12, 2016: 7:00pm-8:30pm – Fairfax Campus, Johnson Center, Room 334

The State of Vaccine Skepticism in Maps
Typically, we look at graphs of vaccine exemptions, but you can now explore vaccination confidence throughout the world via interactive maps. A recent study looked at public confidence in vaccines, asking 66,000 people in 67 countries their thoughts and beliefs in vaccines. Researchers found that France was the least confident in vaccine safety and that “one peculiar conflict emerges from Southeast Asia, where the public seemingly has little doubt as to the safety, importance, or effectiveness of vaccines, yet may eschew them on religious grounds.” Attitude and confidence in vaccines is strongly correlated with vaccine exemptions or refusal. As we saw with California and the Disneyland-associated measles outbreak in 2015, vaccine-preventable disease are becoming a growing issue, not just within the U.S., but on a global level. Since we’re on the topic – make sure to get your annual flu shot as the CDC is recommending people get their flu vaccines before the end of October. You can find more on the 2016/2017 flu season here.

Las Alamos is Now Tracking Global Disease Outbreaks
biosurveillance-map Biosurveillance is a mixed bag of tricks – some prefer focusing on symptoms, others on vectors, but overall, there’s been a steady dispute regarding how best to pursue it. Los Alamos National Laboratory in New Mexico is working to break through the fog and establish a new method “describing disease that is designed to bring this disparate field together and gain international traction. Their new system of classification is called the Anthology of Biosurveillance Diseases, and they have set up an online database to support it.” The new system takes into account many important parts of the epidemiology and biosurveillance practices for disease tracking. Detailed description of vectors, search capabilities by symptoms, and a wide range of synonyms for diseases are all components to this new system. This is no easy task and the system designers know that as new diseases are found or knowledge expands for existing ones, there will be no rest for the wicked. Biosurveillance has so many moving parts and this database is the first step in trying to get them all into one area to better strengthen the surveillance system and thus the capacity for response by public health. While they work to make the updating process automated,  the database has been made available online here.

ISSF Roundtable on Barriers to Bioweapons
If you haven’t read GMU Biodefense Associate Professor Sonia Ben Ouagrham-Gormley‘s Barriers to Bioweapons: The Challenges of Expertise and Weapons Development, get the scoop from this latest review. Dr. Ouagrham-Gormley’s book breaks down the realities behind bioweapons development and that weaponization of biological agents is much more difficult than many realize. Not only is this one of my favorite books, depicting the realities of tacit knowledge as a major roadblock for non-state bioweapons development, but this review gives great insight from multiple subject matter experts from several academic institutions. “The reviewers place Ben Ouagrham-Gormley’s work in the context of the literature on nuclear power and nuclear weapons, and note that she impressively draws from multiple literature, including business school case studies, anthropology, and organizations and management. To these strengths, I would like to add three others: first, Barriers to Bioweapons is well organized and very well written—a model of rich empirics and theoretical sophistication. Second, Ben-Ouagrham-Gormley successfully tackles a large and hard problem: showing how state structures and processes shape specific technical and scientific outcomes. Third, in addition to her excellent discussion of tacit knowledge, Ben Ouagrham-Gormley writes with great insight about knowledge reservoirs, knowledge transfer, and knowledge loss in and across organizations.”

Enhancing International Nuclear Nonproliferation in an Increasingly Dangerous World
GMU Biodefense PhD alum, Daniel M. Gerstein points to the vulnerability of international nuclear nonproliferation and how this U.S. national security strategy is “teetinger on a dangerous precipice.” What can the U.S. do? Between North Korea’s recent nuclear and missile tests and Russian President Vladimir Putin’s halting of the bilateral Plutonium Management and Disposition Agreement with the U.S., the stakes are progressively getting higher. Gerstein notes that new national programs tend to focus on deterrence against regional adversaries and terrorist interest in acquisition of nuclear capabilities hasn’t waned, but rather the interest has grown as proliferation challenges become chronic. He notes several key steps to help reverse these trends – “First and foremost, the United States should reassure allies about the viability of U.S. nuclear security guarantees and the stockpile. The next administration will need to conduct a Nuclear Posture Review to set the country’s nuclear policy for a five- to 10-year period. Second, the United States should emphasize its absolute support for the goals of the Nuclear Non-Proliferation Treaty, or NPT – nonproliferation, disarmament and peaceful uses of nuclear energy. Third, the two most immediate state nuclear proliferation issues must be addressed: Iran and North Korea. On Iran, the United States should build support for the JCPOA, both domestically and across the globe.” International strategies must account for the unpredictable nature and capabilities of North Korea and push for China to increasingly pressure them to abandon their nuclear program.

All Things Zika
After reporting an additional 2,391 cases of locally acquired Zika virus in the first week of September, Puerto Rico is continuing to battle the disease as their case counts top 20,000. Texas is currently enhancing Zika surveillance in the Rio Grande Valley. Brazilian researchers are reporting a constellation of brain injuries from their work with 11 babies whose congenital Zika infections were detected before birth. “Though brain damage varied among the babies, the most common findings were brain atrophy and changes related to disturbances in neuronal migration. Defects ranged from mild brain atrophy and calcifications to severe malformations including absence of the thalamus and lissencephaly. Other findings included hypoplasia of the cerebellum, cerebellar vermis, and corpus callous.” As the outbreak rages on, U.S. public health officials are bracing for the first wave/generation of babies born with Zika-related birth defects. This Generation Zika is expected to be an extraordinary demand on special-needs care. “Data on newborns in Colombia suggests that Zika-infected women who are asymptomatic may give birth to children with Zika-related abnormalities. With that in mind, the U.S. Centers for Disease Control and Prevention has recommended testing for Zika during routine obstetric care for pregnant women who may have been exposed to the virus.” As of October 5th, the CDC has reported 3,818 cases of Zika in the U.S. Hurricane Matthew will be hitting Florida soon and as the state braces for impact, there are growing concerns about the increase of mosquito populations following flooding.

Stories You May Have Missed:

  • Legionnaires’ Outbreak Grows – The Minnesota Department of Health is reporting another spike in Legionnaires’ cases in the midst of an ongoing outbreak. They recently reported 23 new cases, all of which are people who live, work, or spend time in the Minneapolis suburb, Hopkins. “Seven locations with cooling towers have been identified as possible sources. Samples have been collected from those towers. But officials point out that cooling towers are not regulated in Minnesota, so there is no registry or master list of towers.”
  • The Biology of Anthrax Conference- Make sure to check out the upcoming November 15-18 conference in Tampa, Florida. While primarily a sporadic pathogen of herbivores, its use as a bio-terror agent has highlighted its ability to infect humans. This conference aims to bring together investigators active in this area with a view to sharing observations and ideas and fostering new collaborations and synergies. Participants at previous conferences in Cardiff in 2009 and 2014 included representatives from academia, industry, policy makers and government.

Pandora Report 9.23.2016

by spopescu, posted in Pandora Report

Welcome to the first few days of Fall 2016! We need to really ramp up our investment in vaccines – an ounce of prevention is worth a pound of cure. Doctors in Saskatchewan are imploring the province to declare a medical state of emergency over a surge of HIV/AIDS cases. Johns Hopkins University is currently working on a study to assess why healthcare workers catch the flu – what’re your thoughts? Poor PPE use, isolation precautions, and/or hand hygiene is my guess. New research from the World Bank shows that antibiotic resistance is likely to increase poverty and by 2050, could cause global economic damage on par with the 2008 financial crisis. The Blue Ribbon Study Panel on Biodefense has received a $1.3 million grant to continue work on assessing American biodefense systems, informing policymakers, etc. Before we start with the latest in global health security, you can now access (for free!) the Global Health Impacts of Vector-Borne Diseases workshop summary here.

The Uncertain Future of Plum Island 
Established in 1945, Plum Island Animal Disease Center (PIADC) (Orient Point, NY), “has served as the nation’s premier defense against accidental or intentional introduction of transboundary animal diseases (a.k.a. foreign animal diseases) including foot-and-mouth disease (FMD). PIADC is the only laboratory in the nation that can work on live FMD virus (FMDV). The lab and its staff of nearly 400 employees provide a host of high-impact, indispensable preparedness and response capabilities, including vaccine R&D, diagnostics, training, and bioforensics among others.” Not immune to controversy or a theme in horror movies, Plum Island is a research facility that hosts BSL-2, BSL-3 Enhanced, and Animal Biosafety Level 3 and Biosafety Level 3 Agriculture laboratories and animal research facilities that maintain highly restricted access and trained security professionals. The nostalgia of Plum Island is fast approaching as the research center is set to be closed within the next decade. The research campus will move to Kansas and the 840-acre island is up for sale. “Located 100 miles east of New York City, with sweeping water views, the island has already drawn unsurprising interest from local real estate agents and developers, including, yes, Donald J. Trump. Many people in the area, however, want the island preserved as a nature sanctuary or perhaps a park. In July, a coalition of environmental groups and activists filed a federal lawsuit to stop the sale, and there is a similar legislative push in Congress.” Since its inception and through its new ownership in 2003, (when DHS took it over) the biggest concern of Plum Island has always been containment as the infectious livestock samples and animals could introduce diseases, like food-and-mouth disease, to a susceptible population. The facility takes great care to mitigate any risk through “stringent security clearances and background checks, the boiling of all water discarded from the lab and the requirement that anyone who works within the biocontainment lab must shower twice before leaving. As for the cattle, pigs and other animals used for vaccine and other kinds of testing, they are kept in indoor, secured living quarters, said Dr. Luis L. Rodriguez, who leads research at the center’s laboratories.” In the event a deer should swim onto the island, it’s killed and immolated. Aside from the “Island of Dr. Moreau” vibe that is often felt when discussing the island, it has water views and sandy beaches that are met with a green terrain. While the future of the island is up in the air, the zoning stipulates that it must be reconstructed for similar use (i.e. research). Any takers?

Don’t Miss the Biological Threats in the 21st Century Book Launch!
screen-shot-2016-09-12-at-8-00-42-pm On October 14th, join us in celebrating the book launch of Biological Threats in the 21st Century! Biological Threats in the 21st Century introduces readers to the politics, people, science and historical roots of contemporary biological threats through rigorous and accessible chapters written by leading scholars and supplemented by expert point-of-view contributions and interviews. The book launch will feature a panel discussion on the threat of biological weapons and the role of scientists in bioweapons non-proliferation and disarmament. The event is free and open to the public. Lunch will be available beginning at 11:45 AM so please RSVP. Attendants will also be able to pick up the book at a 15% discount.

Screen Shot 2016-04-21 at 1.28.57 PMGMU Biodefense Graduate Program Informational Videos
Curious about a graduate degree in biodefense but unable to attend an information session? We’re happy to show off our new informational videos on both our MS and PhD biodefense programs at GMU. Check out what students are saying about our MS programs (we have both an online and an in-person tract) and our PhD program. You’ll also get to hear from biodefense guru and graduate program director, Dr. Koblentz, throughout the videos!

Bioresearch Labs and Inactivation of Dangerous Pathogens Hearing                                   

The Committee on Energy and Commerce, Subcommittee on Oversight and Investigations will be holding a hearing today at 9am regarding bioresearch labs and the inactivation of dangerous pathogens. While witnesses are by invitation only, the hearing webcast will be available here – don’t miss it! You can also read a recent GAO report on high-containment laboratories: improved oversight of dangerous pathogens needed to mitigate risk. 

The Global Implications of Antibiotic Resistance
I love a good zombie movie like the next person, but where are the horror movies about antibiotic resistance? Show me a film that depicts the global threat of losing all effective antibiotics – that is a real horror movie. The UN General Assembly held a high level meeting on Wednesday about the growing threat of antimicrobial resistance (AMR). Despite increasing surveillance and high-level attention to the rise of the resistant bugs, it will take more than the efforts of a few countries. We’ve passed the golden age of antibiotic development and the “pipeline of new antibiotics has been running dry”. Colistin-resistant bacteria continue to sporadically pop up, highlighting that once again, germs know no borders and are skilled in the art of travel. Hopefully, with the recent UN General Assembly meeting, it will send a clear message that the threat of antibiotic resistance is being taken seriously and for more world leaders to really hone in their efforts for surveillance and prevention through the GHSA. Sadly, a recent study found that antibiotic usage hasn’t changed in hospitals, despite the growing threat of AMR. Researchers looked at patient discharge records in over 300 US hospitals between 2006 and 2012 and “found that 55.1% of patients discharged received at least one antibiotic during their stay, with little change in that proportion between 2006 and 2012. The overall rate of antibiotic use for all study years was 755 days of therapy per 1,000 patient-days, a rate that also saw little change over the period of the study. But the study also showed significant increases in the use of carbapenem antibiotics, third- and fourth-generation cephalosporins, beta-lactam/beta-lactamase inhibitor combination antibiotics, tetracyclines, and vancomycin.”

Next Generation Global Health Security Network Webinar – Our Antimicrobial Anthropocene: UNiting against Pan-Epidemic AMR
As you know, a key component of responding to (and preparing for) outbreaks is the ability to treat them. But how can we make sure that the drugs we have to treat diseases will work? How can we combat the growing trend of antimicrobial resistance? In line with the recent high-level meetings by the Presidential Advisory Committee (see here) and the UN, the Next Generation Global Health Security Network is pleased to present the first of an ongoing series of webinars, this one focused on Antimicrobial Resistance (AMR). These webinars are intended to provide unique learning opportunities for global health security professionals through educational sessions about important GHS topics and situate emerging issues for a global health audience.  Please join the event on Tuesday, September 27 from 6:00-7:00pm EST as the Next Generation Global Health Security Leaders Network and CRDF Global host a webinar by Dr. Dan Lucey titled “Our Antimicrobial Anthropocene: UNiting against Pan-Epidemic AMR”.  There will also be limited in-person space for those in the DC metro area who wish to attend.  If you wish to attend in person, please RSVP by email (nextgenghsa@gmail.com)

Your Weekly Dose of Zika News
The Zika virus outbreak has pointed out several international challenges when it comes to infectious disease outbreaks – funding, vector control, long-term health effects, and international events. Sandro Galea points to the poet John Keats as a potential role model for how we should approach such events. Trained as a surgeon, Keats had a solid background in the scientific method, however the quality he “emphasized was not the scientist’s finely tuned analytic instrument, but the ability to exist comfortably amidst uncertainty and doubt.” Galea notes that the Zika outbreak is a prime example of how scientists should start thinking more like poets, living in the space of inevitable ambiguity and the new norm of the grey area. Here is the ECDC’s epidemiological update on Zika. The CDC is ramping up testing support in Florida to aid in rapid diagnostics. A recent study published in the Lancet points to a low risk of sexual transmission and questions the sustainability of Zika transmission without the presence of a vector. The CDC is reporting 3,358 cases of Zika virus in the US as of September 21st. Of these cases, 43 are locally acquired related to mosquitoes.

Stories You May Have Missed:

  • Are We Prepared For Another Ebola Outbreak? In response to last week’s Ebola and Zika: Cautionary Tales article, John LaMattina is digging into the realities of R&D. “Actually, a check of clinicaltrials.gov lists 71 studies ongoing in Ebola, the majority of which involve studying novel vaccines or drugs in humans. Furthest along appears to be Merck with planned regulatory filings for its vaccine in 2017.” He notes that while Ebola may not be making headlines, that shouldn’t be translated into a total lack of preparedness for another outbreak. You can also read the latest article in Nature – Public Health: Beating Ebola.
  • Glory in the Guts- If you’re a fan of Mary Roach’s books (Stiff, Spook, etc.), you’ll love hearing what GMU Biodefense MS student, Greg Mercer, thinks of her latest book, Grunt. Roach’s latest book looks at the life of soldiers and how the military keeps them alive. “The only gun that interests her is the one that fires chicken carcasses at military aircraft to test their birdstrike resilience. Roach isn’t squeamish, though. She participated in a training simulation as a victim of smoke inhalation burns, experienced a live-fire demonstration of the importance of hearing protection, and endured a treadmill trip in the 104-degree “cook box” to witness just how easy it is to become dehydrated while lugging 80 pounds of gear.”
  • Global Capacity for EID Detection – In the most recent CDC Emerging Infectious Disease online report, researchers are evaluating the global improvements of disease detection and communication during 1996-2014. “Improvement since 1996 was greatest in the Eastern Mediterranean and Western Pacific regions and in countries in the middle HDI quartiles. However, little progress has occurred since 2010. Further improvements in surveillance will likely require additional international collaboration with a focus on regions of low or unstable HDI.”