Combination therapy with cadonilimab, a first-in-class bispecific antibody targeting both PD-1 and CTLA-4, and chemotherapy offers encouraging antitumor activity and manageable safety as a first-line treatment for patients with advanced esophageal squamous cell carcinoma (ESCC), according to findings from a phase 2 study (NCT05522894).1
The trial successfully met its primary end point, achieving an objective response rate (ORR) of 81.4% (95% CI, 66.6%–91.6%) and a disease control rate (DCR) of 97.7% (95% CI, 86.2%–99.9%) The median progression-free survival (PFS) was 7.10 months (95% CI, 5.68–8.48), with overall survival (OS) data still immature.
The authors note that the ORR of 81.4% is numerically superior to the 69.3%–72.1% rates reported in phase 3 trials of PD-1 inhibitors plus chemotherapy (ESCORT-1st2 and JUPITER 063), though they caution that cross-trial comparisons should be interpreted with care due to differences in patient populations.1
Notably, the treatment showed significant efficacy across all patient subgroups, irrespective of PD-L1 expression levels. Patients with a low PD-L1 combined positive score (CPS) of < 1 achieved an ORR of 87.5% (95% CI, 47.9%–99.7%) and a median PFS of 8.41 months, suggesting the combination could be a potent new option for a difficult-to-treat population.
Study Overview and Rationale
The trial was designed to address the unmet need for more effective first-line treatments for advanced ESCC, a malignancy with a poor prognosis. While the current standard of care—a PD-1/PD-L1 inhibitor combined with chemotherapy—has improved outcomes, a significant portion of patients do not achieve durable responses.
“The blockade of both PD-1 and CTLA-4 strengthens the tumor immune response and achieves an effect more than merely additive,” study authors wrote.
The study was an open-label, single-arm, multicenter phase 2 study conducted in 3 hospitals in China. The primary end point was ORR, with PFS, DCR, OS, and safety as secondary end points.
A total of 43 patients were enrolled between February 2023 and April 2024. All patients had an ECOG performance status of 0 or 1 and had not received prior systemic treatment for advanced disease.
The treatment regimen consisted of a combination phase of 10 mg/kg cadonilimab administered intravenously (IV) on day 1 of a 21-day cycle and paclitaxel or nab-paclitaxel and cisplatin on day 1. This was continued for up to 6 cycles. Following this phase, patients continued with cadonilimab monotherapy every 21 days until disease progression, unacceptable toxicity, or a maximum of 24 months.
Safety and Tolerability Profile
The safety profile of cadonilimab plus chemotherapy was considered manageable, with no new or unexpected safety signals observed. All 43 patients (100%) experienced a treatment-related adverse event (TRAE) of any grade; 53.5% (n = 23) of patients experienced a grade 3 or 4 TRAE. No grade 5 TRAEs occurred.
All-grade immune-related AEs (IRAEs) were observed in 19 patients (44.2%). Grade 3 to 4 IRAEs occurred in 5 patients (11.6%).
TRAEs led to the discontinuation of cadonilimab in 7 patients (16.3%).
Exploratory Biomarker Analysis: DNA Methylation
The study conducted an exploratory analysis of cell-free DNA (cfDNA) methylation as a potential biomarker for treatment response, yielding highly significant results.
A unique 5-gene methylation panel (APBA2, EPAS1, TRIM58, ITPKA, LINC00554) was identified that could stratify patients into response groups. The average methylation level of this 5-CpG signature before treatment robustly predicted outcomes. A higher baseline methylation level (hypermethylation) was significantly associated with nonresponders (P <.001).
Using a 35% methylation level as a threshold, patients with < 35% baseline methylation had a 100% response rate (19 of 19 achieved partial response). Patients with >35% baseline methylation had only a 35.3% response rate (6 of 17 responded).
Posttreatment analysis revealed that responders tended to have stabilized methylation levels, while non-responders exhibited global hypomethylation. This suggests that cfDNA methylation could serve not only as a static predictive biomarker but also as a dynamic tool for real-time monitoring of tumor-immune interactions.
REFERENCES:
1. Qu W, Gao J, Zhang B, et al. Cadonilimab combined with taxane and cisplatin as the first-line treatment of advanced esophageal squamous cell carcinoma: an open-label, multicenter phase II trial. J Immunother Cancer. 2025 Oct 30;13(10):e012869. doi: 10.1136/jitc-2025-012869.
2. Luo H, Lu J, Bai Y, et al. Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial. JAMA. 2021; 326:916–25.doi:10.1001/jama.2021.12836
3. Wang Z-X, Cui C, Yao J, et al. Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial. Canc Cell. 2022; 40:277–88. doi:10.1016/j.ccell.2022.02.007
Morning everyone. Households could begin receiving free solar power for a few hours each day, even if they don’t have panels installed, under a new federal government plan.
Plus: Sussan Ley has no good choices in the net zero stoush, a Queensland professor wins the prime minister’s science prize for her work on Covid, Melbourne Cup punts remain popular, and Jennifer Lawrence reveals why she’s not going to “fuel the fire” over Donald Trump.
Australia
Prof Lidia Morawska has won the $250,000 prime minister’s prize for science. Photograph: The Prime Minister’s Prizes for Science
‘Pioneering’ | Prof Lidia Morawska, an expert in air quality and health at Queensland University of Technology, has won the top $250,000 prime minister’s science prize for her “pioneering research” that helped change the way the world treated the Covid pandemic.
Free power | Australian households in three states will get access to at least three hours a day of free solar power, regardless of whether they have rooftop panels, the federal government has announced.
Coalition crunch | Sussan Ley is under intense pressure to drop Liberal party support for net zero targets after the Nationals came out against the idea, threatening the Coalition partnership.There are no good options for Ley, according to our political editor, who writes that she faces either losing voters or losing the backing of many MPs.
Custody death | An inmate who suffered a seizure was put in handcuffs and a spit hood by prison guards who left him naked in an “at-risk cell” before he died two days later, an inquest in Northern Territory has heard.
Sure bet | Australians are still gambling as much as ever on the Melbourne Cup despite polls saying people are losing interest in the famous race. But betting patterns are changing.
World
Jennifer Lawrence says she no longer wants to comment on the Trump administration. Photograph: Vianney Le Caer/Invision/AP
‘Fuel to a fire’ | Jennifer Lawrence has said she no longer feels it appropriate to speak out against the Trump administration, lest she exacerbate unhelpful debate and further divisions. Follow developments in the US here.
‘Such a huge crime’ | Navi Pillay, the South African judge who was the chair of the UN inquiiry into Gaza, tells Guardian Australia why her panel concluded that Israeli action in Gaza was genocide and why the world must fight Israel’s actions in the same way as it took on apartheid. A UN security council resolution mandating the introduction of an international stabilisation force into Gaza is likely to be ready within two weeks but faces delays over its makeup.
Rome collapse | A medieval tower in central Rome has partly collapsed twice during renovations, trapping one worker on an upper floor and injuring another. Watch the dramatic footage here.
Stabbing charge | A 32-year-old man has been charged with attempted murder after Saturday’s mass stabbing on a high-speed train in Cambridgeshire in which 10 people were injured. He was also charged with a separate incident earlier in the day that left another person hurt.
Step by step | Even modest amounts of daily exercise such as 3,000 steps a day may slow the progression of Alzheimer’s disease in older people who are at risk of developing the condition, researchers have said.
Full Story
Composite: STF/AFP
The rising resistance to Pine Gap
Nour Haydar speaks to senior reporter Ben Doherty about the rising resistance to Pine Gap, and the questions the spy base raises about Australia’s complicity in alleged crimes abroad.
Full Story
The rising resistance to Pine Gap
In-depth
A shipwreck of a timber-built sailing vessel at Point Lonsdale, Victoria. Photograph: Rodney Nicholson
The discovery of pieces of wood sticking up from the sand on a beach on Victoria’s Bellarine Peninsula sparked much excitement as it emerged that it was a shipwreck buried under the shifting sands for at least 75 years. Stephanie Convery reports on the marine archaeologists trying to solve the mystery of what vessel it was and how it got there.
Not the news
The cover of Thai: Anywhere and Everywhere by Nat Thaipun. Photograph: Hardie Grant
A bumper crop of Australian books hit the stores this month led by the intriguing collaboration between Helen Garner, Chloe Hooper and Sarah Krasnostein on The Mushroom Tapes, Kate Mildenhall’s rural crime thriller and a Thai cookbook by MasterChef Australia 2024 winner Nat Thaipun.
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Sport
The Kangaroos are favourites for the AFLW title. Illustration: Guardian Design
AFLW | North Melbourne are the hot favourites to win back-to-back flags as the finals start this week. Can anyone stop them?
Concussion | The NRL confirmed last night it is assessing whether there was a failure in the application of rugby league’s concussion protocols following Eli Katoa undergoing emergency surgery for a head injury at the weekend.
Cricket | Mark Wood says England are confident as they go into the Ashes and believe they have an Australia-style blueprint to put pressure on the home batting lineup.
Andrew Hastie would run for the Liberal leadership if Sussan Ley is ousted amid an internal Coalition battle over net zero, according to the Sydney Morning Herald. If you’re going to the Melbourne Cup today you’d better pack a poncho, the Herald Sun advises, with inclement weather on the way. Broncos legend Gorden Tallis has joined forces with Matthew Johns in an effort to revitalise the embattled NRL club Gold Coast Titans, the Bulletin reports,
What’s happening today
Racing | Nup to the Melbourne Cup protests in Melbourne, Sydney, Hobart, Brisbane and Perth.
Economy | Reserve Bank chiefs reveal their latest judgment on interest rates at 2.30pm.
Security | Asio chief Mike Burgess delivers the 2025 Lowy lecture at Sydney Town Hall this evening.
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Brain teaser
And finally, here are the Guardian’s crosswords to keep you entertained throughout the day. Until tomorrow.
With an investment of over $1 billion, Deloitte’s unified delivery platform integrates specialized agents and AI- powered tools and proprietary data into client-project workflows, accelerating time to value
NEW YORK, Nov. 3, 2025 /PRNewswire/ — Deloitte announced today updates and new features to its agentic AI-infused delivery platform, Ascend™. The platform enhancements will improve how Deloitte executes and orchestrates work and supports its software, solutions and products for our clients, with a common engineering foundation.
With Deloitte’s continued investment of over $1 billion across agentic and Generative AI capabilities, these new features and capabilities will allow a single-entry point for Deloitte professionals to access this tested, end-to-end delivery method for serving our clients. These enhancements will make it faster and easier for professionals to access Deloitte’s collective intelligence to tailor specific solutions and drive stronger client outcomes.
“With the rapid rise of Generative and agentic AI, our clients want to know that we’re applying the best tools and technology to drive trustworthy results more quickly,” said Jason Salzetti, CEO and chair, Deloitte Consulting LLP. “Ascend enables human and AI collaboration to increase that speed-to-market while also maintaining transparency and security across client deliverables and solutions. With Ascend, we are making it easier for our professionals to apply our insights, agents and workflows to advance our clients’ specific mission and business goals.”
How Ascend Delivers Secure Solutions, Easier Access to GenAI tools
Deloitte’s long history of delivering impactful, trustworthy solutions is the foundation of the Ascend platform. Ascend turns complexity into clarity by equipping teams with the right tools, agents and technologies precisely when needed for maximum impact, enhanced outcomes and minimal friction. Benefits include:
Flexibility across the delivery lifecycle: Ascend codifies the “Deloitte Way” of successful client delivery in a single platform to drive improved project outcomes that apply Deloitte tools, solutions, or approaches for clearly defined project workflows.
Rapid use case development: Ascend works with clients’ existing infrastructure and Deloitte’s vast network of alliance relationships to fit the specific needs of each enterprise. For example, in the platform’s GenAI Lab, professionals can experiment and prototype with the latest GenAI tools.
Built-in security and trust: Ascend was built with Deloitte’s Trustworthy AI™ Framework to help organizations mitigate risks such as bias and improper training to assist clients in scaling their AI deployments with confidence.
Client portal and access: Ascend enables ease of access for clients to the delivery of work through a digital channel and engagement features.
“Ascend provides us with a strong client-centric, market-ready engineering foundation, to modernize the delivery of our services and capabilities while positioning us to respond with speed in this rapidly changing marketplace, using the latest GenAI tools and tech,” said Sundhar Sekhar, national managing principal for offerings and solutions, Deloitte Consulting LLP.
How Ascend enabled a new testing management capability, powered by UiPath
Deloitte clients are already experiencing the benefits of Ascend as a common engineering and project delivery platform as Deloitte teams use this dynamic platform to create smarter, faster and more consistent outcomes.
For example, Deloitte and UiPath, a global leader in agentic automation, collaborated to enhance Ascend by developing a testing management capability, which accelerates activities in the testing lifecycle for large-scale enterprise modernization programs. It combines Deloitte’s proprietary knowledge base with GenAI and agentic automation.
“Deloitte’s testing management capability, built on Ascend and powered by the enterprise-ready agentic testing capabilities of UiPath Test Cloud, delivers broader test coverage, faster time to value, and reduced business disruption. It can help organizations achieve a significant reduction in their overall test lifecycle efforts,” said Gerd Weishaar, general manager and senior vice president of product management, UiPath Test Cloud.
“What makes this collaboration so compelling is the vision: bringing agentic testing to life, where AI agents work hand-in-hand with testers to drive speed, resilience, and innovation at scale. Together with Deloitte, we’re helping enterprises set a new standard for how testing is done in the AI era.”
Deloitte has been at the forefront of AI innovation for over a decade, expanding its offerings through its Generative AI practice, including Converge™ by Deloitte, a leading suite of AI-driven industry solutions and Zora AI™ by Deloitte, an agentic product platform offering a suite of ready-to-deploy digital workers. With its Deloitte Ascend™ delivery platform, Deloitte technologists, developers and engineers build and deliver new AI solutions, agents and tools for its clients and people. Deloitte aims to transform and modernize its services and future offerings – all based on its deep industry knowledge and specialized experience across domains. Deloitte integrates AI following its Trustworthy AI™ framework to manage industry and sector-specific risks. Additionally, Deloitte enhances AI fluency, investing in global learning and trainings through the Deloitte AI Academy™.
About Deloitte Deloitte provides industry-leading audit, consulting, tax and advisory services to many of the world’s most admired brands, including nearly 90% of the Fortune 500® and more than 8,500 U.S.-based private companies. At Deloitte, we strive to live our purpose of making an impact that matters for our people, clients, and communities. We bring together distinct talents, technologies, disciplines, and an ecosystem of alliances to help tackle today’s most complex business challenges and drive long-term progress. Deloitte is proud to be part of the largest global professional services network serving our clients in the markets that are most important to them. Bringing more than 180 years of service, our network of member firms spans more than 150 countries and territories. Learn how Deloitte’s approximately 470,000 people worldwide connect for impact at www.deloitte.com.
Deloitte refers to one or more of Deloitte Touche Tohmatsu Limited, a UK private company limited by guarantee (“DTTL”), its network of member firms, and their related entities. DTTL and each of its member firms are legally separate and independent entities. DTTL (also referred to as “Deloitte Global”) does not provide services to clients. In the United States, Deloitte refers to one or more of the US member firms of DTTL, their related entities that operate using the “Deloitte” name in the United States and their respective affiliates. Certain services may not be available to attest clients under the rules and regulations of public accounting. Please see www.deloitte.com/about to learn more about our global network of member firms.
Baker McKenzie has advised One Equity Partners and its portfolio company, Trustmarque Group, a leading technology services partner, on the merger between Trustmarque and Ultima Business Solutions, a premier managed services provider owned by Apse Capital. Upon completion, the combined business will form a leading IT channel powerhouse in the UK.
The transaction will mark a transformative milestone, bringing together a combined Gross Invoiced Income (GII) expected to reach GBP 1 billion. With a proposed unified workforce of over 1,000 employees, the combined business will be poised to unlock greater innovation, agility, and market impact. This planned strategic alignment not only strengthens operational capabilities but also sets the stage for bold growth, deeper customer engagement, and a shared vision to lead the industry with purpose and performance. Together, the combined businesses will provide a comprehensive portfolio of expert driven, end-to-end IT solutions and managed services with pioneering IP at the core. From One Equity Partners, Andrew Dunn (Partner) and Vittorio Palladino (Principal) will remain on the board of the combined business.
The Baker McKenzie team was led by Private Equity Partner, Justin Hutchinson, with support from Private Equity Associates Angus Duncan, Emma Burton and Francesca Cohen. The team also included Debt Finance Partner, Nick O’Grady; Tax Partner, Natalie Dunne; and Antitrust & Competition Partner, Anthony Gamble.
Commenting on the deal Justin Hutchinson, said: “We’re proud to have supported One Equity Partners and Trustmarque on this transformative transaction, which brings together two highly respected businesses in the UK technology services space. This deal highlights our strength in advising private equity sponsors and their portfolio companies on complex mergers and acquisitions, particularly in the technology and business service sectors.”
Thank you, David. I appreciate the opportunity to speak again at the Brookings Institution.1 It is always an honor for me to return to the place where I held my first job as an aspiring economist. I had the good fortune to be a research assistant for the eminent economist and public servant, including as Vice Chair of the Fed, Alice Rivlin early in my career. It was a formative, if not transformative, experience for me, and I remain grateful to her and Brookings for it.
Today, I would like to speak to you about how I see the U.S. economic outlook evolving, specifically through the lens of the dual mandate given to the Federal Reserve by Congress to promote maximum employment and price stability. Then, I will discuss how my assessment of the outlook guides my thinking on monetary policy.
I will start by acknowledging that, due to the government shutdown, this is a challenging time to give an economic outlook speech. Federal statistical agencies, including the Bureau of Labor Statistics, the Census Bureau, and the Bureau of Economic Analysis, have not produced many of the data I regularly use in assessing the economy, such as monthly employment data from BLS and the personal consumption expenditures (PCE) price index from BEA. The longer the shutdown lasts, the more data could be disrupted.
Economic Outlook
However, we are not flying blind. The staff at the Federal Reserve and I use a wide variety of data from administrative sources and various private-sector providers to continually evaluate the state of the economy in real time. That practice has become essential in recent weeks given the lack of official releases. These data include alternative measures of inflation, labor-market activity, and production and spending, inflation. For example, states continue to report data on unemployment insurance (UI) claims, and online job boards provide data on available positions. Various firms provide pricing data on a variety of products and services, including housing and vehicles, and offer information on credit card spending, the moods of consumers and employers, and manufacturing and service-sector output. In my first speech as a Governor in 2022, I encouraged the use of more high-frequency, real-time data from the private sector, and I think this has borne fruit.2 And, of course, the Reserve Banks in the Fed System are a rich source of statistical and anecdotal data, some of which are documented in the Beige Book report policymakers receive before each Federal Open Market Committee (FOMC) meeting.
In addition, I find broad outreach to business leaders, workers, nonprofits, and families around the country essential in understanding the state of the economy. I will rely on this outreach, these alternative data sources, and the latest available federal data when discussing my outlook today.
Inflation
First, I will turn to inflation. Based on the available data for September, it is estimated that the PCE price index rose 2.8 percent in the 12 months ending in September, significantly above our 2 percent target. Core inflation, which excludes the volatile food and energy categories, was also estimated to be 2.8 percent. Both of these readings are as high or higher than their readings a year before, propped up by an increase in tariff-affected goods prices.
My outreach to business leaders suggests that the pass-through of tariffs to consumer prices is not yet complete. Many firms have adopted a strategy of running down their inventories at lower price levels before raising prices. Others have reported waiting until tariff uncertainty is resolved before passing increases on to consumers. New car models, clothing lines, and other products will be coming onto the market, and that process will continue to provide firms with an opportunity to level set prices. As such, I expect inflation to remain elevated for the next year.
Nonetheless, the effect of tariffs on prices, in theory, should represent a one-time increase. It is encouraging that most long-run inflation expectations, including from the New York Fed Survey of Consumer Expectations, are low and stable at this juncture. When excluding tariff effects, 12-month core PCE inflation through September appears to be about 1/2 percentage point lower at about 2.3 percent, suggesting that underlying inflation has continued to make progress toward target. My assessment is that inflation is on track to continue on its trend toward our target of 2 percent once the tariff effects are behind us. The big caveat is that tariff effects must prove not to be persistent and that monetary policy remains appropriately focused on achieving that goal.
This is a point worth dwelling on for just a moment. The FOMC’s firm commitment to its inflation mandate is imperative to ensure that inflation does remain in check, as I do expect in my baseline forecast. So let me be clear. I am committed to reaching our 2 percent inflation target. Moreover, I will be prepared to act forcefully, if the tariff effects appear to be larger or last longer than expected, or if other evidence emerges that higher levels of inflation are becoming entrenched in expectations.
Labor market
I will now turn to the labor market. We have less recent official data on the labor market, but the latest available indicators suggest that the labor market remains solid, though gradually cooling. The unemployment rate edged up over this summer from 4.1 percent in June to 4.3 percent in August, a relatively low reading one would expect to see in a healthy economy. To put 4.3 percent into perspective, the average unemployment rate over the 50-year period preceding the pandemic was 6.2 percent. Since August, more recent labor-market indicators, such as UI claims, job postings, and individuals’ assessments of job availability, signal little change to the August reading—at most a small uptick. Taken together, the slightly rising unemployment rate indicates the labor market is softening, but only modestly so.
I would be remiss if I did not mention slowing in payroll gains observed over the summer. In most cases, a sharp slowing in payrolls would suggest increasing slack and would generally be accompanied by an increase in the unemployment rate. However, in this instance, the slowing in payrolls can mostly be explained by a coincident decline in population growth due to immigration policy. Because they are currently driven by fluctuations in population growth, the payroll numbers do not provide a definitive signal about labor-market slack. Therefore, it would be prudent for us to consult the other indicators I already mentioned.
It is important to recognize that there appear to be worsening outcomes for vulnerable and low-to-middle-income (LMI) households. In the labor market, youth and Black unemployment rates, both of which tend to be more cyclical than total unemployment, have steadily risen since this spring through the latest readings in August. The deteriorating labor market experienced by these two vulnerable groups mirrors other emerging strains in some households’ financial health and balance sheets. Among LMI households, we have observed large increases in delinquencies, especially last year, and there is some evidence that their spending has stagnated, in particular compared to the robust spending growth of their higher-income counterparts. This is sometimes called a “two-speed” economy, when the well-off are doing well, while LMI and vulnerable households are not.
Monetary policy works by affecting conditions for the entire economy and is not well suited to produce specific outcomes for specific groups of people. Ultimately, I believe delivering on our dual-mandate goals will produce the best outcomes for all Americans. Nonetheless, it is important for policymakers to monitor the two-speed economy. Understanding the challenges faced by so many Americans underscores the reasons why we need to get monetary policy right. Vulnerable and LMI households are the ones who will be the first and most hurt, if the labor market were to suddenly deteriorate or if inflation were to remain too high.
Economic activity
To turn to economic activity, recent readings are consistent with solid overall growth. Output has been supported by household consumption that has held up better than expected earlier this year. Yet, what has been more striking is the strength of business investment. Business investment has been driven by investment in high-tech equipment and software, seemingly mostly related to AI. As I have mentioned in previous speeches, that suggests to me there is a reason to be sanguine about future productivity growth.3 I see AI as a general-purpose technology, on par with the steam engine and the personal computer, that has the potential to transform the economy and boost productivity. I expect this sector to continue to provide support to output growth over the next few years, at least.
In the very near term, I see the federal government shutdown as weighing on activity this quarter. Furloughing federal workers and forgoing government purchases of goods and services, including those provided by contractors, directly lowers output in the public sector. And spillover effects to the private sector are worth considering. Potential delays in government payments, permits, inspections, insurance provision and other functions could slow certain spending and investment activities, and some small business contractors with very little cushion may never be paid and may ultimately close their businesses. I see both sets of effects as being largely temporary. It is anticipated that they would unwind in the following quarter after the shutdown ends.
In summary, after a temporary slowdown due to the government shutdown, I expect the economy to grow moderately over the medium term, supported by an AI productivity boom. I see the labor market as still solid, but I am highly attentive to downside risks. I see inflation as remaining somewhat elevated due to tariff effects and subject to upside risks.
Monetary Policy
Having articulated my outlook, I will turn to my current view of monetary policy. At the FOMC meeting last week, I supported the Committee’s decision to lower the target range for the fed funds rate by a quarter-point to 3-3/4 to 4 percent. I viewed that decision as appropriate, because I believe that the downside risks to employment are greater than the upside risks to inflation. I view the latest reduction in the fed funds rate as another gradual step toward normalization. I see the current policy rate as remaining modestly restrictive, which is appropriate given that inflation remains somewhat above our 2 percent target.
At last week’s meeting, I also supported the decision to conclude the reduction of the aggregate securities holdings on the balance sheet on December 1. The long-stated plan had been to stop balance sheet runoff when reserves were somewhat above the level the Committee deemed consistent with ample reserve conditions. In the several weeks ahead of our latest meeting, signs, such as an increase in repo rates relative to administered rates, did emerge suggesting this standard had been reached. These developments were anticipated as the size of the balance sheet declined and supported the decision to cease runoff.
Looking ahead, policy is not on a predetermined path. We are at a moment when risks to both sides of the dual mandate are elevated. Keeping rates too high increases the likelihood that the labor market will deteriorate sharply. Lowering rates too much would increase the likelihood that inflation expectations will become unanchored. As always, I determine my monetary policy stance each meeting based on the incoming data from a wide variety of sources, the evolution of my outlook, and the balance of risks. Every meeting, including December’s, is a live meeting.
Thank you again for the opportunity to return to Brookings. I look forward to our conversation.
1. The views expressed here are my own and not necessarily those of my colleagues on the Federal Open Market Committee. Return to text
2. Lisa D. Cook (2022), “Economic Outlook,” speech delivered at the Peterson Institute for International Economics, Washington, D.C., October 6. Return to text
3. See Lisa D. Cook (2024), “What Will Artificial Intelligence Mean for America’s Workers?” speech delivered at the Ohio State University, Columbus, Ohio, September 26. Return to text
Vaccination is one of the most effective tools for preventing infectious diseases in both humans and animals. Safe and effective vaccines reduce mortality, improve productivity and protect communities from zoonotic diseases that can cross species barriers. However, the success of vaccination programs depends not only on the quality of vaccines produced but also on how they are stored, transported and handled. When vaccines are exposed to temperatures outside their recommended range, their potency can decline, leading to a failure to generate adequate immune protection. Such failures can erode public trust when vaccinated individuals, both human or animal, still fall ill with the targeted disease.
Maintaining vaccines within the correct temperature range from the point of manufacture to administration is therefore critical. The temperature-controlled system that preserves vaccine potency along the travel route is known as the cold chain. A robust cold chain ensures that vaccines remain active and efficacious until their expiry date, forming the backbone of successful immunisation and vaccination programs.
Public health systems worldwide devote substantial resources to building and maintaining cold chain infrastructure. An effective cold chain requires three key elements. First, personnel: trained staff to manage vaccine storage and distribution at every point in the system, ensuring that handling protocols are consistently applied. Second, equipment: reliable refrigeration and transport equipment capable of maintaining required temperatures, together with temperature-monitoring devices that allow real-time oversight. Third, procedures: standardised protocols that guide proper equipment use, temperature monitoring, and the safe transport and storage of vaccines.
When any of these components fail, whether due to lack of training, power outages or equipment breakdowns, the integrity of vaccines can be compromised. For this reason, continuous investment in cold chain systems is not optional but essential for sustaining vaccine confidence and effectiveness.
While public health vaccination programs often receive strong institutional and financial support, animal health services in many low- and middle-income countries remain under-resourced. The consequences are significant: inadequate cold chain capacity can lead to unreliable vaccine supplies, loss of potency and high mortality from diseases that are otherwise preventable.
These weaknesses in animal health systems have several important wider implications. Livestock owners who experience disease outbreaks following vaccination may lose confidence both in vaccines and in veterinary health care services. High animal mortality can make it difficult to detect outbreaks early, diminishing the sensitivity of surveillance systems. Poor disease surveillance allows zoonotic pathogens — that is, those that can infect both animals and humans — to circulate unnoticed in animal populations, potentially spilling over into human communities. Finally, these outbreaks may have serious negative impacts on household livelihoods and national economics.
As a consequence, inadequate investment in animal health cold chains not only affects livestock productivity but also undermines public health security and food systems.
Encouraging progress has been made in Bangladesh, where a community-based One Health initiative funded by the USAID Feed the Future Bangladesh Livestock and Nutrition Activity and UK Research and Innovation-funded One Health Poultry Hub has highlighted the benefits of shared responsibility across sectors. A farmer survey conducted under the Bangladesh Livestock and Nutrition Activity revealed very low levels of vaccination coverage. This finding was presented at a national meeting that brought together public health, animal health and environmental health officials, along with local government representatives, reflecting the essence of the One Health approach, which seeks to balance and optimise the health of people, animals and ecosystems through cross-sectoral collaboration.
Public health officials were surprised to learn about the low coverage of livestock vaccination for two key reasons. Firstly, in rural districts facing high child undernutrition, improving access to nutrient-rich animal-source foods is seen as vital. Second, frequent high mortality in animals reduces surveillance sensitivity and timely disease outbreak reporting. Rather than attributing blame to veterinary services, they expressed readiness to support joint action. Proposed areas of collaboration included cold chain training, shared maintenance responsibilities and coordinated monitoring of livestock vaccination coverage. They further recommended that animal vaccination data, particularly for zoonotic and high-priority diseases, be routinely shared with District Public Health Nutrition Committees. This integration would help raise awareness of challenges in veterinary health systems and strengthen links between animal health and human nutrition initiatives.
Importantly, discussions also explored the potential for shared cold chain infrastructure. Public health facilities in Bangladesh now possess well maintained refrigeration units, backup power generators and trained personnel. Public health officers felt that, with proper coordination, these existing structures could benefit veterinary vaccination programs — and were keen to take this idea forward. (While the World Health Organization prohibits human and animal vaccines from being stored in the same refrigerator, this barrier can be overcome by installing separate storage units powered by a unified electricity source and shared backup systems.)
This example from Bangladesh illustrates the value of the One Health approach in addressing common logistical challenges. In many contexts, animal health and public health services operate in parallel, each maintaining their own infrastructure, staff and supply systems. However, greater efficiency and resilience can be achieved through integrated planning and resource sharing. Beyond Bangladesh, this idea is also being considered in the four countries participating in the West African One Health project — Sierra Leone, Guinea, Liberia and Nigeria — which aims to strengthen the mitigation and prevention of outbreaks and address sectoral inequities through increased multisectoral collaboration.
In fact, the Guinean National Health Security Agency is currently coordinating with the National Directorate of Veterinary Services regarding the storage and distribution of dog rabies vaccine. In Guinea, rabies vaccines are distributed through a tiered system to maintain cold chain integrity. Vaccines are first stored at four regional veterinary laboratories, then transferred to refrigerators within the Prefectural Directorates of Livestock, and subsequently to human health centres at the sub-prefectural level. Transport is conducted using coolers with regularly-replaced ice packs. Most health centres are equipped with solar-powered refrigerators. Coordination between the Expanded Vaccination and Primary Health Care Program and the National Directorate of Veterinary Services ensures effective management and safety of animal vaccinations.
Access to potent vaccines, safe food and effective disease control underpins both human and animal health. Yet sustaining these systems requires collaboration across sectors that have traditionally worked in isolation. The One Health approach offers a pragmatic and equitable framework for doing so. By sharing cold chain resources — equipment, expertise and maintenance systems — countries can strengthen both public and veterinary health services while maximising the impact of limited resources. In short, investing together means saving together: protecting livestock, safeguarding people and securing the health of the ecosystems we all depend on.
Between 2012 and 2022, a national target of 4 million STEM degrees earned in the United States was surpassed by 16%, cumulatively totaling 4.65 STEM degrees over that decade. This exceeded a projected need of 4 million, which was one million more than the baseline projection.
Degree-completion rates for STEM undergraduates have improved to now match or even exceed those of non-STEM peers in many cohorts.
Representation of Hispanic students and women in STEM undergraduate programs has shown notable gains. But significant gaps remain for Black students and American Indian and Alaska Native students.
The study emphasizes that keeping and improving national‐level data collection is critical for sustaining STEM education progress and policy oversight.
A recent analysis of national higher-education data by a researcher at the University of California, Santa Cruz, found that the United States exceeded the goal of producing one million more graduates in the fields of science, technology, engineering, and mathematics (STEM) over the course of a decade. That goal, set in a 2012 report by then-President Barack Obama’s Council of Advisors on Science and Technology (PCAST), was one of several national objectives created to maintain America’s scientific leadership position in an increasingly competitive global landscape.
The analysis, by National Science Foundation postdoctoral fellow Haider Ali Bhatti was, on the one hand, good news: It indicates that the expansion of programs intended to support STEM education outcomes in the years following the report’s publication yielded a successful return on investment.
But at the same time, Bhatti’s study serves as a warning about the danger of tearing down federal institutions and the information infrastructure they provide. His findings underscored the vital importance of keeping and improving national-level data collection for sustaining STEM education progress and establishing policies and priorities that aim to maintain U.S. leadership in an increasingly competitive scientific and economic landscape.
Let the data speak
The study is framed in the present-day context of the growing challenges faced by U.S. universities: public skepticism of their value, claims of ideological indoctrination, and the ongoing dismantling of diversity, equity, and inclusion initiatives.
Haider Ali Bhatti
“These criticisms demand higher education research to demonstrate tangible outcomes of progress informed by evidence-based evaluations,” said Bhatti, in UC Santa Cruz’s Department of Ecology & Evolutionary Biology. “In this climate of heightened public scrutiny, undergraduate STEM education offers a particularly valuable disciplinary domain to assess higher-education outcomes given its importance to national workforce development goals and global economic competitiveness.”
Relying largely on data from the National Center for Education Statistics (NCES), Bhatti found that the number of STEM degrees obtained in the decade following the 2012 “Engage to Excel” report exceeded the goal of an additional million graduates by 16%. He also found that the proportion of STEM degrees among all degrees conferred increased over the decade, reversing previous declining trends.
Stemming economic threats
In addition, STEM employment expanded correspondingly, with growth surpassing the PCAST report’s projections, according to Bhatti. In his study, he explained how the 2012 report emerged as a response to specific workforce and educational concerns facing the country in the years prior. While America had historically relied on foreign-born STEM professionals to satisfy unmet workforce demands, the presidential advisory council warned that this strategy was no longer sustainable.
STEM education and employment opportunities were increasing globally, making other countries potentially more attractive to STEM-trained workers and creating potential vulnerabilities for American economic stability, the study states. Furthermore, other research showed that STEM-related jobs represented some of the best opportunities for upward mobility in the American economy, offering high wages and lower unemployment rates than other sectors.
The 2012 report concluded that expanding access to these high-quality careers provided a potential pathway to reduce income inequality if more Americans were trained in STEM fields. Against this backdrop of global competition and domestic opportunity, PCAST established concrete, measurable goals to address what the report characterized as a critical “decision point” for American educational and economic leadership at the time of its publication.
Other encouraging and stubborn trends
In his study, Bhatti cited other research that analyzed national data to assess progress on two other goals in the PCAST report: improving retention rates among students in STEM fields, and increasing demographic representation. At the time of the report, only 40% of students who started as STEM majors graduated with a STEM degree. To assess progress on that front, Bhatti presented results from research that analyzed longitudinal cohort data from the ongoing Beginning Postsecondary Students (BPS) study by NCES.
That research found improved retention rates among bachelor’s degree students in STEM fields, at 52%, along with a phenomenon that Bhatti said is more powerful: retention rates in STEM that were equal to or higher than those in non-STEM fields at the bachelor’s degree level. Given the typical amount of exploration and changing of majors that undergraduates do, Bhatti said it was encouraging to see comparatively less attrition in STEM disciplines than in other fields.
In regards to increasing demographic representation, Bhatti reported mixed progress, with national data showing substantial gains for Hispanic students and women, but also persistent gaps for Black and American Indian/Alaska Native students. According to NCES data, the share of Hispanic STEM degree recipients increased from 9.5% to 14.7%.
Bhatti also found that the percentage of science and engineering degrees earned by women rose from 43% to 49% at the associate’s level, while remaining stable at about 50% for bachelor’s degrees over the past decade.
But overall, NCES data show an upward trend for women in STEM: Between 2012 and 2022, the share of women who earned STEM degrees increased steadily from just under 32% (124,853) to over 37% (193,625).
Refuting critics with proof of ROI
Besides NCES, Bhatti examined other national reports, data sets, and longitudinal studies spanning over 10 years since the publication of the PCAST report. And now, more than a decade later, he said if higher education’s critics are correct, we would expect minimal to no progress toward these goals. But his study clearly showed otherwise.
“Overall, these results reveal patterns that challenge public narratives about the diminishing state of higher education—particularly in undergraduate STEM education,” Bhatti concluded. “These findings provide an evidence-based foundation for both evaluating past investments and guiding future strategies to strengthen America’s talent development in the evolving global STEM ecosystem.”
Bhatti emphasized that NCES is a division of the U.S. Department of Education, which has been critically defunded and affected by mass layoffs due to federal restructuring. “This work shows the importance of data infrastructure to check if we, as a nation, are on track in the increasingly competitive world of STEM,” he said. “We need things like NCES to enable evidence-based evaluations of our educational progress.”
While his study is largely positive about recent trends in undergraduate STEM education, Bhatti also noted several caveats. The decade covered by his study included large‐scale reforms as well as variability across institutions and regional systems. Thus, Bhatti said national averages may have masked pockets of underperformance.
In addition, while degree production and completion have improved, Bhatti’s findings stop short of documenting the quality of the learning experience, the alignment of degrees with workforce needs, or long‐term career outcomes. He points out that “degree counts alone are insufficient; we must also ask whether graduates are succeeding in the jobs of today and tomorrow.”
His analysis, “One million more: assessing a decade of progress in undergraduate STEM education,” originally appeared in the journal Journal of Microbiology & Biology Education on August 21.
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A brewer plans to open up a 150-year-old bottle of beer, made for an Arctic expedition, so a modern version can be created.
The original Allsopp’s Arctic Ale was bottled in Burton-upon-Trent for Sir George Nares, when he set out to reach the North Pole in 1875.
It was later discovered in a box in a garage in Gobowen, Shropshire, and sold at auction for £3,300 in 2015.
The buyer was Dougal Gunn Sharp, founder and master brewer of Edinburgh-based Innis & Gunn, and he now plans to use the ale to seed a new limited-edition beer.
Samuel Allsopp & Sons in Burton-upon-Trent designed the beer for sailors enduring temperatures as low as -40C and it had an alcohol strength of about 9%.
The beer was said to resist freezing because of its unfermentable sugars and it had six times the calorie content of conventional beer.
It was used on a number of British Arctic expeditions and records from the time said it was dark brown and so thick it had to be lifted from the brewing copper in buckets.
Mr Sharp plans to work in partnership with Allsopp’s Brewery on the new beer, which will be called Innis & Gunn 1875 Arctic Ale.
He said: “Some people might think it’s madness to open it, but I think the real madness would be to leave it sitting on a shelf.
“Beer is meant to be shared, particularly on this, its 150th anniversary.”
Mr Sharp also said there was “something very special” about being able to taste a “piece of brewing and maritime history”.
Jamie Allsopp, founder of the revived Allsopp’s Brewery and a direct descendant of Samuel Allsopp, said there was “something uniquely romantic about Allsopp’s Arctic Ale”.
He said the beer was “one of the strongest and most extraordinary beers ever made” and he said when he was first approached by Mr Sharp with the idea of making a new version “I honestly thought he was mad.”
The idea of using the original beer to create a new one was “a kind of alchemy”, he said.
The new beer will be released later this year, with a small number of hand-bottled examples sold through a ballot.
