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+ + + +IMMUNERECOV CONTRIBUTES TO IMPROVEMENT OF RESPIRATORY AND IMMUNOLOGICAL RESPONSE IN POST-COVID-19 PATIENTS. - Conditions: Long Covid19; Dietary Supplements; Respiratory Tract Infections; Inflammation
Interventions: Dietary Supplement: Nutritional blend (ImmuneRecov).
Sponsors: Federal University of SĂŁo Paulo
Recruiting
Study on Post-Acute COVID-19 Syndrome in Improvement of COVID-19 Rehabilitated Patients by Respiratory Training - Conditions: COVID-19, Post-Acute COVID-19 Syndrome, Dyspnea, Incentive Spirometer
Interventions: Device: breathing training
Sponsors: Tri-Service General Hospital
Active, not recruiting
Physical Activity Coaching in Patients With Post-COVID-19 - Conditions: Post-COVID-19 Syndrome
Interventions: Behavioral: Self-monitoring; Behavioral: Goal setting and review; Behavioral: Education; Behavioral: Feedback; Behavioral: Contact; Behavioral: Exercise; Behavioral: Report; Behavioral: Social support; Behavioral: Group activities; Behavioral: World Health Organization recommendations for being physically active
Sponsors: University of Alcala; Professional College of Physiotherapists of the Community of Madrid
Not yet recruiting
Ensitrelvir for Viral Persistence and Inflammation in People Experiencing Long COVID - Conditions: Long COVID; Post Acute Sequelae of COVID-19; Post-Acute COVID-19
Interventions: Drug: Ensitrelvir; Other: Placebo
Sponsors: Timothy Henrich; Shionogi Inc.
Not yet recruiting
Low-intensity Aerobic Training Associated With Global Muscle Strengthening in Post-COVID-19 - Conditions: COVID-19
Interventions: Procedure: muscle strengthening
Sponsors: Centro UniversitĂĄrio Augusto Motta
Completed
Intravenous Immunoglobulin Replacement Therapy for Persistent COVID-19 in Patients With B-cell Impairment - Conditions: COVID-19
Interventions: Drug: Immunoglobulins
Sponsors: Jaehoon Ko
Not yet recruiting
Effect of Inhaled Hydroxy Gas on Long COVID Symptoms - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Device: Hydroxy gas
Sponsors: Oxford Brookes University
Recruiting
Community Care Intervention to Decrease COVID-19 Vaccination Inequities - Conditions: COVID-19 Vaccination
Interventions: Behavioral: Community Health Worker Intervention to Enhance Vaccination Behavior (CHW-VB)
Sponsors: RAND; Clinical Directors Network; National Institute on Minority Health and Health Disparities (NIMHD)
Recruiting
PROmotion of COVID-19 BOOSTer VA(X)Ccination in the Emergency Department - PROBOOSTVAXED - Conditions: COVID-19
Interventions: Behavioral: Vaccine Messaging; Behavioral: Vaccine Acceptance Question
Sponsors: University of California, San Francisco; National Institute of Allergy and Infectious Diseases (NIAID); Pfizer; Duke University; Baylor College of Medicine; Thomas Jefferson University
Not yet recruiting
Evaluating a Comprehensive Multimodal Outpatient Rehabilitation Program for PASC Program to Improve Functioning of Persons Suffering From Post-COVID Syndrome: A Randomized Controlled Trial - Conditions: Post-Acute COVID-19; Post-Acute COVID-19 Syndrome; Post-Acute COVID-19 Infection; Long COVID; Long Covid19; Dyspnea; Orthostasis; Cognitive Impairment
Interventions: Other: Comprehensive Rehabilitation; Other: Augmented Usual Care
Sponsors: University of Pennsylvania; Medical College of Wisconsin; National Institutes of Health (NIH)
Not yet recruiting
Multilevel Intervention of COVID-19 Vaccine Uptake Among Latinos - Conditions: Vaccine Hesitancy
Interventions: Behavioral: Multilevel Intervention
Sponsors: San Diego State University
Not yet recruiting
Stem Cell Study for Long COVID-19 Neurological Symptoms - Conditions: Post-Acute COVID-19 Syndrome
Interventions: Biological: Stem Cell
Sponsors: Charles Cox; CBR Systems, Inc.
Not yet recruiting
Pursuing Reduction in Fatigue After COVID-19 Via Exercise and Rehabilitation (PREFACER): A Randomized Feasibility Trial - Conditions: Long-COVID; Long Covid19; Post-COVID-19 Syndrome; Post-COVID Syndrome; Fatigue
Interventions: Other: COVIDEx
Sponsors: Lawson Health Research Institute; Western University
Not yet recruiting
An ncRNA transcriptomics-based approach to design siRNA molecules against SARS-CoV-2 double membrane vesicle formation and accessory genes - CONCLUSION: Our novel in silico pipeline integrates effective methods from previous studies to predict and validate siRNA molecules, having the potential to inhibit viral replication pathway in vitro. In total, this study identified 17 highly specific siRNA molecules targeting NSP3, 4, and 6 and accessory genes ORF3a, 7a, 8, and 10 of SARS-CoV-2, which might be used as an additional antiviral treatment option especially in the cases of life-threatening urgencies.
Elevated peripheral levels of receptor-interacting protein kinase 1 (RIPK1) and IL-8 as biomarkers of human amyotrophic lateral sclerosis - Amyotrophic lateral sclerosis (ALS) is a devastating fatal neurodegenerative disease with no cure. Receptor-interacting protein kinase 1 (RIPK1) has been proposed to mediate pathogenesis of ALS. Primidone has been identified as an old drug that can also inhibit RIPK1 kinase. We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1^(G93A) mice and ALS patients. SOD1^(G93A) mice treated with primidone showed significant delay of symptomatic onset and improvedâŠ
Development of iminosugar-based glycosidase inhibitors as drug candidates for SARS-CoV-2 virus via molecular modelling and in vitro studies - We developed new iminosugar-based glycosidase inhibitors against SARS-CoV-2. Known drugs (miglustat, migalastat, miglitol, and swainsonine) were chosen as lead compounds to develop three classes of glycosidase inhibitors (α-glucosidase, α-galactosidase, and mannosidase). Molecular modelling of the lead compounds, synthesis of the compounds with the highest docking scores, enzyme inhibition tests, and in vitro antiviral assays afforded rationally designed inhibitors. Two highly activeâŠ
Enhancement efficiency delivery of antiviral Molnupiravir-drug via the loading with self-assembly nanoparticles of pycnogenol and cellulose which are decorated by zinc oxide nanoparticles for COVID-19 therapy - The target of the study is to modify the efficiency of Molnupiravir-drug (MOL) for COVID-19 therapy via the rearrangement of the building engineering of MOL-drug by loading it with self-assembly biomolecules nanoparticles (NPs) of pycnogenol (Pyc) and cellulose (CNC) which are decorated by zinc oxide nanoparticles. The synthesis and characterization of the modified drug are performing successfully, the loading and release process of the MOL drug on a nano surface is measured by UV-VisâŠ
Combating DC-SIGN-mediated SARS-CoV-2 dissemination by glycan-mimicking polymers - Many viruses exploit the human C-type lectin receptor dendritic cell-specific ICAM-3 grabbing nonintegrin (DC-SIGN) for cell entry and virus dissemination. An inhibition of DC-SIGN-mediated virus attachment by glycan-derived ligands has, thus, emerged as a promising strategy toward broad-spectrum antiviral therapeutics. In this contribution, several cognate fragments of oligomannose- and complex-type glycans grafted onto a poly-l-lysine scaffold are evaluated as polyvalent DC-SIGN ligands. TheâŠ
Discovery of High Affinity Cyclic Peptide Ligands for Human ACE2 with SARS-CoV-2 Entry Inhibitory Activity - The development of effective antiviral compounds is essential for mitigating the effects of the COVID-19 pandemic. Entry of SARS-CoV-2 virions into host cells is mediated by the interaction between the viral spike (S) protein and membrane-bound angiotensin-converting enzyme 2 (ACE2) on the surface of epithelial cells. Inhibition of this viral protein-host protein interaction is an attractive avenue for the development of antiviral molecules with numerous spike-binding molecules generated toâŠ
Molybdenum Nanodots for Acute Lung Injury Therapy - Acute respiratory disease syndrome (ARDS) is a common critical disease with high morbidity and mortality rates, yet specific and effective treatments for it are currently lacking. ARDS was especially apparent and rampant during the COVID-19 pandemic. Excess reactive oxygen species (ROS) production and an uncontrolled inflammatory response play a critical role in the disease progression of ARDS. Herein, we developed molybdenum nanodots (MNDs) as a functional nanomaterial with ultrasmall size,âŠ
Levocetrizine attenuates cyclophosphamide-induced lung injury through inhibition of TNF-α, IL-1ÎČ, TGF-ÎČ and MMP-9 - Cyclophosphamide (CP) is an antineoplastic drug commonly used worldwide. Despite its spread, it causes fatal organ toxicity. Lung toxicity is a serious side effect of CP. Actually, in the past three years the world has been facing an un-predicted crisis following COVID-19 pandemic and the associated high-mortality rates attributed to respiratory distress. Accordingly; this study aimed to probe the potential prophylactic role of levocetrizine against CP-induced lung injury. Animals were allocatedâŠ
Peroxides Derivatives as SARS-CoV-2 Entry Inhibitors - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Host cell invasion is mediated by the interaction of the viral spike protein (S) with human angiotensin-converting enzyme 2 (ACE2) through the receptor-binding domain (RBD). In this work, bio-layer interferometry (BLI) was used to screen a series of fifty-two peroxides, including aminoperoxides and bridged 1,2,4 - trioxolanes (ozonides) classes, with the aim ofâŠ
Bile acids and bile acid activated receptors in the treatment of Covid-19 - Since its first outbreak in 2020, the pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) has caused the death of almost 7 million people worldwide. Vaccines have been fundamental in disease prevention and to reduce disease severity especially in patients with comorbidities. Nevertheless, treatment of COVID-19 has been proven difficult and several approaches have failed to prevent disease onset or disease progression, particularly in patients with comorbiditiesâŠ.
Antimicrobial activity of silver-copper coating against aerosols containing surrogate respiratory viruses and bacteria - The transmission of bacteria and respiratory viruses through expelled saliva microdroplets and aerosols is a significant concern for healthcare workers, further highlighted during the SARS-CoV-2 pandemic. To address this issue, the development of nanomaterials with antimicrobial properties for use as nanolayers in respiratory protection equipment, such as facemasks or respirators, has emerged as a potential solution. In this study, a silver and copper nanolayer called SakCuÂź was deposited on oneâŠ
An ACE2 decamer viral trap as a durable intervention solution for current and future SARS-CoV - The capacity of SARS-CoV-2 to evolve poses challenges to conventional prevention and treatment options such as vaccination and monoclonal antibodies, as they rely on viral receptor binding domain (RBD) sequences from previous strains. Additionally, animal CoVs, especially those of the SARS family, are now appreciated as a constant pandemic threat. We present here a new antiviral approach featuring inhalation delivery of a recombinant viral trap composed of ten copies of angiotensin-convertingâŠ
Analysis of SARS-CoV-2 Variant-Specific Serum Antibody Post-Vaccination Utilizing Immortalized Human Hepatocyte-Like Cells (HLC) to Assess Development of Immunity - CONCLUSION: HLC, along with AT-2 cells, provides a useful platform to study the development of neutralizing antibodies post-vaccination. Vaccination with the 3 available vaccines all elicited neutralizing serum antibodies that inhibited binding of each of the variant spike proteins to both AT-2 and HLC cells. This study suggests that inhibition of spike binding to target cells may be a more useful technique to assess immunity than gross quantitation of antibody.
Quercetin improves and protects Calu-3 airway epithelial barrier function - Introduction: In light of the impact of airway barrier leaks in COVID-19 and the significance of vitamin D in COVID-19 outcomes, including airway barrier protection, we investigated whether the very common dietary flavonoid quercetin could also be efficacious in supporting airway barrier function. Methods: To address this question, we utilized the widely used airway epithelial cell culture model, Calu-3. Results: We observed that treating Calu-3 cell layers with quercetin increasedâŠ
Main and papain-like proteases as prospective targets for pharmacological treatment of coronavirus SARS-CoV-2 - The pandemic caused by the coronavirus SARS-CoV-2 led to a global crisis in the world healthcare system. Despite some progress in the creation of antiviral vaccines and mass vaccination of the population, the number of patients continues to grow because of the spread of new SARS-CoV-2 mutations. There is an urgent need for direct-acting drugs capable of suppressing or stopping the main mechanisms of reproduction of the coronavirus SARS-CoV-2. Several studies have shown that the successfulâŠ
Can Guatemalans Save Their Democracy? - Months after the election, President-elect Bernardo ArĂ©valoâs path to taking office remains uncertain. - link
How Hamas Used Sexual Violence on October 7th - Physicians for Human Rights Israel issued a report collecting evidence of sexual and gender-based violence. One of its authors lays out their findings. - link
Looking for a Greener Way to Fly - The Treasury Department is about to announce tax credits for sustainable aviation fuel, which raises the question: What fuels are actually âsustainableâ? - link
Colorado Reconsiders Letting Trump on the Ballot - A Colorado Supreme Court case is one of several considering whether Trump should be disqualified under the Fourteenth Amendment, but it has proceeded the furthest. - link
The War in Gaza Has Been Deadly for Journalists - The president of the Committee to Protect Journalists explains why Israelâs military campaign has led to an unprecedented number of deaths among members of the press in just two months. - link
+Two decades after 9/11, extremist groups continue to pull off surprise attacks. Why? +
++On August 6, 2001, George W. Bush was given what may be the most infamous daily intelligence brief ever received by a US president. It was titled âBin Ladin Determined to Strike in US,â and it included details on the activities of al-Qaeda operatives in the US, including threats to hijack US aircraft. In response, Bush did virtually nothing. And then, a little over a month later, those predictions came stunningly true with the 9/11 attacks. +
++Bush would not be the last leader to ignore such a warning. Decades into the âwar on terror,â itâs clear that political leaders, as well as some of the worldâs most powerful militaries and intelligence, still underestimate the ability and ambition of extremist militant groups to carry out large-scale attacks. There have now been three major instances of such failures in the past decade. +
++Multiple news outlets, including the New York Times and Haaretz, have now reported that Israeli intelligence agencies had provided officials with extraordinary details about the plans for what became the October 7 attack more than a year before it was carried out. Just a day before the attack, the CIA reported unusual activity by Hamas in Gaza, suggesting an imminent military operation. Hamas militants reportedly trained for the attack in all but plain sight less than a mile from the Israeli border. +
++Yet Israeli officials appear to have dismissed these warnings, believing the group had scaled back its military ambitions to the occasional rocket barrage. Instead of reinforcing the border with Gaza, they chose to focus Israelâs military assets on other threats, including Hezbollah in Lebanon and the increasingly restive West Bank. Ultimately, some 1,200 Israelis would pay for this miscalculation with their lives, as would thousands more Palestinian civilians in the war that has followed. +
++But the October 7 attack was far from the first instance of this kind of strategic surprise from an extremist militant group in recent years. In 2014, the terrorist group then known as the Islamic State in Iraq and Syria (ISIS) began taking over towns in western Iraq. Even after the group had seized the city of Fallujah, the site of the bloodiest battles of the Iraq War, President Barack Obama felt comfortable using a flip sports metaphor to dismiss ISIS as an amateur imitation of al-Qaeda. âIf a jayvee team puts on Lakers uniforms that doesnât make them Kobe Bryant,â he told the New Yorker that January. +
++Six months later, the âjayveesâ had taken over Mosul, Iraqâs largest city, were threatening Baghdad, and had proclaimed the establishment of a âcaliphateâ that, at its height, would control a territory the size of Great Britain. The US launched a military intervention to defeat the group in Iraq and eventually in Syria as well. US troops remain in both countries today â as does ISIS, which is still active, albeit much diminished. +
++In August 2021, the world was stunned again as the Taliban marched into Kabul, meeting almost no resistance as an Afghan state propped up with tens of billions of dollars in American funding collapsed and US personnel â along with thousands of Afghans â scrambled to evacuate. +
++While an eventual Taliban victory was not shocking in itself â the group had been steadily gaining territory in the lead-up to a planned US troop withdrawal â few expected it to happen so rapidly. A month before the withdrawal, President Joe Biden told reporters at the White House that he trusted âthe capacity of the Afghan militaryâ and said he believed that the Afghan leaders âclearly have the capacity to sustain the government in place.â He made these statements despite increasingly dire warnings from US intelligence agencies that the Afghan military was likely to collapse. While senior administration officials later said these assessments were made with a low degree of confidence, the reality is that the evacuation of Kabul would descend into chaos, including a bombing that killed 13 US service members and more than 160 Afghans. +
++These are three very different examples involving very different countries and militant groups. But in all these cases, extremist militant groups demonstrated previously unseen ambition and destructive capabilities. And in all three cases, governments ignored or dismissed warning signs of an impending catastrophe until it was too late. +
++Analysts and former intelligence agents who spoke with Vox say that a combination of cognitive biases, cultural prejudices, and bureaucratic inertia cause such warnings to be ignored time and again. But just because these problems are well-known does not mean they are easy to address. And given the terrible toll from fighting terror over the past two decades â in lives, dollars, and lost civil liberties, especially for Muslims â the price of success may be just as high as the cost of failure. +
++The problem of surprise isnât a new one in intelligence-gathering, nor one unique to extremist groups. In 1962, RAND Corporation analyst Roberta Wohlstetter wrote a classic account of the intelligence failure leading up to the Pearl Harbor attack in 1941. It concluded that, though the US military had collected abundant information suggesting an impending attack â including intercepts of decoded Japanese diplomatic cables that indicated preparations for a major rupture in US-Japan relations â they were hampered by diplomatic inertia and a failure to detect the relevant signals within all the noise. +
+ ++âIf our intelligence systems and all our other channels of information failed to produce an accurate image of Japanese intentions and capabilities, it was not for want of the relevant materials,â Wohlstetter wrote. âNever before have we had so complete an intelligence picture of the enemy.â +
++That scenario â too much information, not enough understanding of which bits are actually important â has occurred over and over again in the history of intelligence failures, from the outbreak of the Korean War to the Tet Offensive in the Vietnam War to 9/11. Erik Dahl, a former naval intelligence officer and a professor at the Naval Postgraduate School, said that the high-tech surveillance tools available to todayâs spies have, in some ways, only made the problem worse. According to a 2019 estimate, the National Security Agency intercepted and stored an average of 1.7 billion emails, phone calls, and other communications every day. +
++âWe have too much information and not enough understanding of whatâs going on in the world,â Dahl told Vox. As an example, he pointed to the failed 2009 Christmas Day âunderwear bombingâ attack. A White House review later concluded that intelligence analysts had collected enough data to disrupt the plot, but did not act on it because the information was âfragmentary and embedded in a large volume of other data.â The plot only failed because the bomb failed to detonate. +
++The problem is compounded when the information counteracts a governmentâs political preferences. Famously, the George W. Bush administration cherry-picked only the information that supported its preferred narrative when it was building the case for invading Iraq. That was a case of political leaders hearing what they want in order to hype up a nonexistent threat. But political preferences can also cause them to ignore a real one. +
++Obama had been elected in large part because of his pledge to take troops out of Iraq. Biden had vowed to bring Americaâs long and frustrating war in Afghanistan to a close. Benjamin Netanyahuâs government had argued that the security threat from Hamas militants in Gaza was contained and the country could focus on other political priorities. Some Israeli officials even believed there was an advantage to having a group like Hamas in power, as it reduced pressure on Israel to negotiate over the establishment of a Palestinian state. In each case, warnings of an impending attack were highly inconvenient for the governmentâs preferred course of action â and thus, tended to be downplayed. +
++âHuman beings are really, really good at shaping the facts to support their own opinions,â said Emily Harding, a former CIA analyst now at the Center for Strategic and International Studies. +
++Religiously motivated, underground, non-state militant groups also pose a particular challenge when state-run intelligence agencies try to analyze their intentions. +
++âIt is difficult for modern Western intelligence services and national security organizations, which are created and established largely to track other entities that look like themselves, to get a handle on the problem of subnation states or non-state actors,â said Dahl. +
++Shiraz Maher, co-director of the International Centre for the Study of Radicalisation at Kingâs College London, pointed out that religiously motivated groups often act with a different set of cost-benefit concerns than secular ones. Hamas, for instance, was willing to carry out its attacks despite every indication that it would ultimately result in massive casualties for both its own fighters and Palestinian civilians. (Israel claims to have killed 5,000 of Hamasâs fighters, while estimates are that more than twice as many Palestinian civilians have been killed. Even if the number of Hamas casualties has been exaggerated, itâs safe to say the groupâs military losses have been substantial.) +
++âThese are rational groups,â Maher said. âBut at the same time, theyâre rational from a completely different epistemic, sociological, philosophical, ideological premise.â +
++Extremist militant groups, by definition underground organizations that emphasize secrecy and demand fierce adherence to their cause, are also notoriously difficult for intelligence services to infiltrate, compared with traditional national governments. They also tend to issue a lot of threats, making it difficult to know which plots they actually intend on, or are capable of, carrying out. +
+ ++Harding, who served at the CIA during the rise of ISIS, says that because extremist groups donât look like traditional militaries, itâs easy to believe they lack the ability to carry out grandiose plans. âThe intent is always there with these groups. Its capability is what you have to measure,â she said. âThey look like a ragtag group of misfits. They donât look like what we think of as a very capable fighting force.â +
++In each of these cases, the failure was not only in predicting the actions of the terrorist group, but in the ability of the terroristsâ opponents to meet the threat once it materialized. In Iraq and in Afghanistan, the United States overestimated the ability of the militaries they had spent years and billions of dollars training and arming, and, perhaps even more important, the willingness of those militaries to fight back. +
++âThe psychology and motivation of a military force: Thatâs the most difficult thing to assess in intelligence,â said Robert Grenier, former director of the CIAâs Counterterrorism Center. âAnybody who tries to make a prediction about that isnât very likely to be successful.â +
++Conversely, in the runup to the war in Ukraine, US intelligence agencies gathered and publicized what turned out to be stunningly accurate information about Russian intentions and battle plans, but failed to predict the capability and resolve of Ukrainian forces in meeting that threat. +
++The October 7 Hamas attacks were different, in part because Hamas is a very different group. In addition to being a militant organization, itâs a governing authority that administers services for more than half a million people and has relations with multiple other states. Itâs also engaged in what it views as a nationalist resistance fight, unlike groups such as al-Qaeda or ISIS. Yet Israel was caught off guard by Hamasâs assault, in part because in the months before October 7, Israel relocated military forces away from Gaza, counting on electronic surveillance, autonomous systems, and relatively small groups of troops to deal with whatever threats might emanate from the strip. The Israelis clearly viewed Hamas as a manageable problem, rather than the impending catastrophe it has turned out to be. +
++âI think it shows thereâs clearly a kind of arrogance on the part of the state,â said Aki Peritz, a former CIA counterterrorism analyst now at American University. +
++In an essay for Foreign Affairs written before the October 7 attacks â but published shortly after â National Security Adviser Jake Sullivan described the Middle East as âquieter than it has been for decades.â Itâs a line likely to age about as well as Obamaâs junior varsity team quip about ISIS. +
++Sullivanâs description might be wishful thinking, but the desire to focus on other priorities is hardly irrational. In recent years, leaders of both parties in the United States have argued that, with the threat from groups like al-Qaeda and ISIS vastly diminished, the country should shift the focus of its national security policy to âgreat power competitionâ with countries like Russia and China. +
++But some terrorism analysts say the attack by Hamas, a group largely written off as a serious threat by both Israel and the United States, shows that we may have been premature in dismissing the ability of groups that have threatened major attacks to actually turn those plans into reality. +
++âI do a lot of work with the US government, including with the intelligence community,â said Colin Clarke, a terrorism analyst with the Soufan Group, a security consultancy. âWeâve talked a lot about ISIS, about al-Qaeda and its respective affiliates, about far-right groups, QAnon, you name it. I hadnât heard anybody mention the name âHamasâ in about 10 years. It wasnât on anybodyâs radar.â +
++The October 7 attack, Clarke said, was a âparadigm shift in how we think about the capabilities of these groups. He added: âWeâve kind of written these guys off, because the big names are gone,â referring to globally famous terrorist leaders like Osama Bin Laden and Ayman al-Zawahiri. +
++Extremist militant groups certainly didnât disappear with the decimation of al-Qaedaâs senior leadership and the destruction of ISISâs caliphate. In many parts of the world, they are growing rapidly. West Africa, for instance, saw more than 1,800 terrorist attacks resulting in nearly 4,600 deaths in just the first half of this year. But the prevailing assumption has been that these groups are mainly concerned with local conflicts rather than transnational attacks. +
++History has shown, however, that local threats donât always stay local. Al-Qaeda in the Arabian Peninsula, the groupâs Yemeni offshoot, was largely thought of as a local group until it very nearly pulled off the failed âunderwear bomberâ plot of 2009. ISIS, at its height, carried out numerous high-profile and deadly attacks in Europe. +
++âWe have batted zero in terms of correctly predicting when a group decides to shift from local to global,â said Katherine Zimmerman, a terrorism analyst at the American Enterprise Institute. +
++Going forward, Israel has vowed that its massive military response to October 7 will wipe out Hamas as a military threat, but these groups can almost never be eliminated entirely. And senior officials, including Gen. Charles Q. Brown, Americaâs new top military commander, have expressed concerns that the scale and brutality of the operation could end up creating more terrorists than it eliminates. Discussing the war in Gaza in a recent CNN interview, Democratic Congressman Seth Moulton cited a study commissioned by retired US Gen. Stanley McChrystal which found that for every civilian killed, about 10 future fighters are recruited. +
++Whatever soul searching goes on in intelligence agencies in the wake of these failures, the answer is clearly not to go straight back to a September 12, 2001, mindset. Western governments, including the United States, have very good reasons for wanting to turn the page on the war on terror. Over the past two decades, the desire to eliminate terrorist threats has led the US into long, bloody, and frustrating wars and a troubling expansion of the surveillance state and discrimination against Muslim Americans. And itâs worth remembering that for every successful attack or military offensive by an extremist militant group, there are many more that never come to fruition. Itâs simply neither possible nor desirable for a society to be on full alert at all times. No one wants to go back to the days of color-coded terror alerts. +
++But after three significant failures in the past decade to predict a major attack by an extremist militant group, itâs clearly a mistake to assume that these groups are no longer capable of surprising and outwitting the worldâs most powerful and technologically advanced states, particularly when, as in the Israeli case, the preparations for that attack are happening in plain view of the state. And thereâs no reason to assume it wonât happen again. +
++âThe curse of the intelligence officer is that we constantly get blamed for bringing the doom and gloom,â said Harding. âThereâs a piece, I think, of human psychology, where you do not want to believe that something truly bad will happen.â That is one mistake that governments canât afford to keep making. +
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+Volunteers could speed up the race for a cure that works for adults as well as children. +
++Few forces have killed off talented people before their time with quite the effectiveness of tuberculosis. Thereâs Chekhov, Chopin, Orwell, Kafka, Keats, Thoreau, Emily BrontĂ« â all brought down by the bacterium before they reached the age of 50. +
++Their ranks are still growing. About 1.3 million people died of TB in 2022, and while deaths were falling pre-pandemic, the Covid-19 era saw progress stall. At this point, its annual death toll exceeds that of HIV/AIDS or malaria. The one vaccine against it was created in 1921 and does not protect adults or adolescents. +
++Yet the world has not mustered much in the way of resources against the disease. The New York Timesâs Stephanie Nolen notes that $5.8 billion a year in treatment funds and $1 billion a year in research funds goes to fighting TB in low- and middle-income countries. By contrast, the equivalent figure for HIV/AIDS treatment is about $20 billion annually. Thatâs a worthy cause, of course, but considering its enormous death toll, TB has drawn the short straw. +
++To some degree, the relative neglect of TB (including by me â I write much more about malaria) has to do with the scale of the challenge it poses. +
++TB is a hard disease to vaccinate against. While most vaccines target viruses, TB is a bacterium, and one with a strange lifecycle. In the vast majority of people it infects, it is âlatent,â not causing symptoms or becoming contagious. The population of people carrying around latent TB infections is truly massive. A recent study compiling blood test estimates found that about 24 percent of people on Earth have TB, with rates ranging from 12â14 percent in Europe and the Americas to over a third in Africa and Southeast Asia. +
++A small share of people with these latent infections (from 5 to 15 percent) develop symptomatic, contagious cases. Often these are treatable with antibiotics â but a significant share of cases are drug-resistant, access to antibiotics is uneven in low-income countries, and mortality is particularly high in people with both HIV and TB. +
++These dynamics complicate the task for a vaccine. Ideally you would want it to both reduce the share of people with latent infections and reduce the odds that those infections become active. But we donât have whatâs called a âcorrelate of protectionâ for TB: a set of indicators of a personâs immune system that show they can resist initial infection, or can keep an infection from becoming active. +
++That makes testing treatments and vaccines tricky â and expensive. Testing needs to be truly massive in scale, given the relatively small share of people who gain new latent infections, or see infections go active, in a given year. M72, the most promising vaccine candidate as of right now, is currently undergoing a phase III trial with a staggering 26,000 participants. It cost donors $550 million to fund it â more than half the annual research budget for TB. And thereâs still a chance it wonât work, or even that the trial wonât pick up enough cases to show anything either way. +
++If every promising TB vaccine costs more than half a billion dollars to test, we are not going to test very many. Even if M72 works, and I very much hope it does, it may still have limitations, as the existing vaccine for children does; and there may be other models that are cheaper to manufacture, or that prove more effective. We want to be testing those, too, and we wonât if testing them is prohibitively expensive. +
++In 2016, the FDA approved a cholera vaccine whose phase III test only included 197 people. Thatâs a tiny fraction of the 26,000 in the TB vaccine trial. This earlier trial was much, much cheaper but still resulted in a working, approved vaccine. +
++What was the trick? The cholera vaccine was assessed using a âchallengeâ trial. 134 of the volunteers in the study actually ingested the cholera bacterium after receiving their vaccine or placebo. Those who got infected were, of course, given antibiotics, fluids, and other necessary treatments. No one got hurt. But their sacrifice enabled researchers to find an effective cholera vaccine for a fraction of the price of a field trial with thousands of people. +
++Human challenge trials are a tested and reliable method, having been used for decades with great success to develop malaria treatments and prophylactics. But they have yet to be used on tuberculosis. Developing a challenge approach takes time, and while that investment has been made for malaria and cholera, it hasnât been for TB yet. Thatâs a shame, because they could provide a way around the huge numbers of people TB trials typically need to detect results. Instead of waiting months for a handful out of a group of thousands of participants to be exposed to TB, researchers could expose several dozen volunteers at once, see how much protection vaccines offer, and proceed from there. +
++This may sound dangerous at first glance, but the risks are small. As with other challenge trials, the researchers would use a weakened or âattenuatedâ version of the pathogen and would provide immediate and comprehensive treatment. One paper examining the idea estimated that a challenge trial would pose a risk of death of about 1 in 1,600, at the high end. For context, thatâs less than half the death risk associated with working as a trucker for five years, and about one-sixth the danger of working as a logger for five years. We let people do those things for money because we value lumber and quick shipping. Thereâs something to be said for letting people take more modest risks to save lives. +
++Luckily, several researchers are trying to develop models for tuberculosis challenges. One would use the 1921 vaccine itself as a substitute for the bacterium, because the vaccine is already in essence an attenuated form of TB. Given that the vaccine is already broadly accepted, it seems hard to argue with the acceptability of this approach. Another option involves an artificial strain of tuberculosis that has been modified to rely on certain compounds that can be withdrawn at any time, effectively offering a âkill switchâ for the bacteria and allowing study researchers to fully cure participants at the end of the trial. Both of these could provide a pathway to challenge trials with extremely minimal risks for participants. +
++Helen McShane, Eric Rubin, Sarah Fortune, and the dozens of other researchers developing these models are, I think, doing some of the highest-impact work in global health right now. But they need help: regular funding, collaborative drug agencies, and a general public thatâs supportive of letting volunteers contribute to the fight against tuberculosis this way. +
++A version of this newsletter originally appeared in the Future Perfect newsletter. Sign up here! +
+Why it isnât the same as chaos. +
++When you think of anarchism, what comes to mind? +
++Maybe you have some vague image of a punk rocker with the Circle-A symbol scratched into her jeans. Or some comic-book supervillain out to destroy the world that spurned him. Those are fun caricatures, but anarchism is actually a rich tradition of thought going back centuries, and it was at the center of utopian leftism until Marxism came along. +
++Today, though, Marxism and other lefty ideologies donât have nearly the purchase they once did, and itâs not entirely clear what, if anything, has filled that void. That lack is all the more interesting given our current moment, when so many conventional ways of doing and thinking about politics are being challenged. +
++So, in that spirit, I invited Sophie Scott-Brown onto The Gray Area to talk about the history of anarchism and its relevance today. Sheâs a research fellow at the University of St. Andrews and the director of Gresham College in London. Sheâs also the author of a new book, Colin Ward and the Art of Everyday Anarchy, which is a fascinating look at the potential of anarchist ideas through the work of the well-known British writer. +
++Below is an excerpt of our conversation, edited for length and clarity. As always, thereâs much more in the full podcast, so listen and follow The Gray Area on Apple Podcasts, Google Podcasts, Spotify, Stitcher, or wherever you find podcasts. New episodes drop every Monday. +
++Weâre all familiar with the stereotypes, but as someone who thinks seriously about anarchism, what does the term mean to you? +
++Yeah, I completely accept the stereotypes. Before you can get to any sort of serious anarchist philosophy, you have to do quite a lot of work deconstructing that for people. So hereâs a working definition that might help. Anarchism, if you just take the very word itself, all it entails is a commitment to a lack of permanent authority. +
++Now, what you then want to do imaginatively after that is wide open. Dare I say thereâs a lot of propaganda out there suggesting there has to be chaos and disorder and violence and crime. But the concept itself simply says no permanent authority, and thatâs about the one thing you can say that really connects up a lot of people who might use that term to describe their beliefs. +
++I heard someone say once that anarchism is âdemocracy taken seriously.â Iâm not sure how accurate that is, but I like it. +
++I think thatâs precisely right. Thereâs a spectrum of anarchisms, so Iâll stress that before I get lots of complaints. However, I would actually argue, philosophically speaking, if youâre going to take that first notion that we started with â that anarchism is a commitment to an absence of permanent authority â that does refine your options a little bit more. +
++Is there a particular species of anarchism that you identify with? +
++I mean, for me, if you want the philosophical roots of it, it comes very much from the Italian rhetorical tradition. So figures like Cicero going through to Vico, people who actually believed that the nuts and bolts of living together means communication, means dispute, means arguing, essentially, but arguing in such a way where the results are not catastrophic. So conflict, I think, is a feature of life. The challenge for us is to not make that conflict catastrophic. +
++So if you accept that conflictâs going to be a ubiquitous feature of life, you say to yourself, âOkay, well, how do I deal with conflict so that itâs not only not catastrophic, but actually creative?â We want to be ambitious with it. We want to know how to live in a world where our conflicts, our differences, our collisions, can be very creative. And that, to me, is the essence of what a full and most radical democratic culture would look like. +
++Do you think itâs better to think of anarchism as a practice rather than an ideology? +
++I certainly do. I think in some ways the big challenge anarchism gives to us these days, and why itâs so removed from where weâre at now but also why itâs going to be essential for the world that weâre going into, is that it comes away from this whole notion that politics always has to have an end game. Itâs going to be a utopia. Itâs going to be the ideal society. There was always an element of utopianism in anarchism, letâs not lie about that, but for me, I feel like weâre reaching times now where people have very little patience with utopian notions. +
++I mean, sure, wouldnât it be nice to live in a world without constant warfare? That kind of utopian thinking has a life and a place, but anything more specific, I think weâve perhaps grown out of that. And therefore this idea of anarchy as a habit of mind or an attitude or a way of thinking and being in the world is useful for thinking about a politics of constant change. Youâve got to think about a politics which accepts that youâre never going to have the truth or the facts or the safe ground under your feet to know youâre right. So how do you live with an ability to adapt? How do you live with contingency? How do you live with the fact that youâre going to be involved in lots of different kinds of problems, probably simultaneously? +
++What would you say is the most promising anarchist idea that seems relevant to this political moment? +
++Decentralization, or the idea that permanent authority is the real bugbear. This is a bit provocative, but even things like codes of law and rights and things like that, they have their purpose and their reason, or they certainly did have their purpose and reason, but increasingly weâre looking at a world where we simply have to get better at taking more responsibility. +
++Anything like government or systems of law, what are they? Theyâre actually heuristics. Theyâre shortcuts for an awful lot of moral and political discussion and reasoning, and people forget that theyâve compressed those discussions into a series of rules of thumb. And we are increasingly not teaching ourselves or troubling ourselves to have those complex conversations between ourselves, and so the tail is sort of wagging the dog now. Weâre becoming very subject to all these systems and structures, which emerged at times that were so unbelievably different from how weâre living now and theyâre not fit for purpose anymore, and so itâs no surprise that theyâre cracking up around us. +
++It does seem like a lot of this comes down to whether or not one views human conflict as ultimately creative or ultimately destructive, whether itâs the beginning of cooperation or the end of conversation. +
++Well, you have the famous quote, itâs usually attributed to Bakunin, âTo destroy and to build again.â There is a vein running through anarchism, which has often been part of the reason why itâs been associated with violence and violent insurrection and chaos and disorder and that sort of thing. But to destroy and to build again can be taken perfectly metaphorically. Itâs this idea that actually destruction and creation are simultaneous things. Any act of creativity is simultaneously destroying some possibilities in favor of others. +
++Every political philosophy, either implicitly or explicitly, is built on a theory of human nature, and I guess Iâm wondering what the anarchist view of human nature is. Or maybe I should ask what your view of human nature is because Iâm sure there are many different views of human nature within the anarchist community. +
++Well, those pesky anarchists, as youâre saying, have pretty much adopted all of the familiar views of human nature and managed to turn anarchism to their advantage in every single possible definition. So you do have those like Peter Kropotkin, the 19th-century Russian anarchist, who are very optimistic about human nature. They think weâre basically social beings and weâre being inhibited or prevented from doing that by these coercive, life-denying, authoritarian structures. Therefore, if we get rid of those, itâll be an easy win. People will find it remarkably easy to be cooperative. +
++But then you have people like Alex Comfort, for example, who is a 20th-century British anarchist who wrote around the 1940s and 1950s, and he took what he called a much more realistic view. He argued that humans arenât going to be like that at all. Theyâre going to collide with each other constantly, so the game in town is how do you manage that conflict? If itâs inevitable, if you canât be too optimistic about everyoneâs social capacity, how can you distribute your society, distribute your decision-making power, distribute your economic power, so nobody ever gets enough to have a critical mass that can overtake everybody else? +
++My view is a total copout, Sean. I think human nature is incredibly malleable. I think it can be many, many, many things. I think weâre like the ultimate actor in neutral, waiting for the next role. +
++Can you be an anarchist and still believe that there are fundamentally evil human beings? +
++Well, I personally donât, which is sometimes really difficult to maintain. I donât believe in evil. What I would say is people certainly have the capacity for it, a shocking capacity for it. And Iâm not a full environmentalist in the sense that I donât think that if only these people had a nice progressive education and lots of drama classes when they were young, everything wouldâve been fine. It mightâve been. In many cases, it probably could have been, but actually we donât quite know what that tipping point is. I would be happier calling it a capacity rather than anything more profound. +
++I do think that human beings are pretty plastic and often we are as good or bad as the world allows us to be. I also believe that evil, for lack of a better word, is a real thing. And I say that as a secular person, not a religious person. And even if we constructed the most practical utopia ever, I think we would still need police and armies. Now, an anarchist might say that people can be wicked, but itâs power that makes them that way. I think thereâs some truth there, but it also seems importantly incomplete. Some people are just wicked whether they have power or not. Would you disagree with that? +
++Well, itâs a big gamble to take, isnât it? I have to ask myself, on balance, is the damage [done by] having things like a permanent police force or a judiciary system skewed in a particular historical social context? Does the damage outweigh the reality that these institutions can actually be the source of so many problems? +
++These arenât easy questions, I get that. I would say that I agree with you that the vast majority of people are not âcruel and disorderedâ when theyâre not governed. I guess I just think that some people are, and the problem is that it doesnât take many cruel and disordered people to make life impossible for everyone else. And that to me is the crucial political problem, how to deal with that. And Iâm not sure anarchy can or does, but I could be wrong. +
++Letâs flip this upside down. Weâre talking about that rare individual who is beyond all reasonable measure, but what we could talk about is all those other people. And I actually think they are really interesting, those other people. Who are they? We donât quite know. +
++But if we take the situation we have now where we have minorities on either end. We have a relative minority of people who are unbelievably kind, youâd call them saintly if you were religious, and then you have the tiny minority of people who weâll call evil for want of any other word. And then you have this sort of spectrum of people in between the two. +
++These are always the really interesting people. Theyâre the people who are very unpredictable, and thatâs wonderful in a way because you never know where theyâll go with a particular issue on a particular day. But theyâll be very responsive to a situational logic rather than some sort of deep ideological commitment to anything. And I think thereâs enormous potential there, which is largely ignored or squandered. +
++People really dismiss everyday sorts of intelligence and reasoning and logic, and because itâs dismissed, because weâre constantly trying to come up with these official measures of what we should be and who we should be, we actually miss that, half the time, weâre perfectly functional anarchists already. +
++Thereâs so much in anarchism that appeals to me, but Iâm not sure it could ever work at scale. And yet you could pose that question about any political order. I fear that one of the lessons of the 20th and 21st centuries might be that humans are not especially equipped to live in large symbolic communities without material connections and shared ways of living. So maybe anarchism could work, but only in smaller, more localized ways? +
++I think thatâs broadly right. This idea that you have to have anarchist nations or even anarchist unions, if you like, well, yes you could, but maybe let them take care of themselves. If they happen, they happen. But what might be more interesting is this notion of being intensely local while being simultaneously global. Iâm trying not to use that old but very useful cliche, âThink global, act local,â but itâs got traction here. +
++Letâs say, for example, that we accept that there are idealistic and ethical and practical reasons why it would be great to see more worker control of industrial democracy in our workplaces. Why is it that we have to retain these fairly doddery, very hierarchical structures of decision-making, which as we know even now are still not particularly diverse? +
++Weâre under so much pressure to keep educating people for longer and longer because now weâre told itâs a lifelong process of learning to keep abreast of everything in order to stay employed. Well, if youâre going to keep this highly educated population, are you honestly going to be surprised when they start getting very resentful about being treated like rube mechanicals in their workplaces? I donât think we need to worry about anarchist nations or anything like that. A much more healthy approach is to start local by giving more workers more control over their lives and their democracy. +
++To hear the rest of the conversation, click here, and be sure to follow The Gray Area on Apple Podcasts, Google Podcasts, Spotify, Stitcher, or wherever you listen to podcasts. +
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