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The Changing Face of Newborn Screening

Thanks largely to genomic advances, an increasing number of advocates are pushing for the use of genome sequencing to improve newborn screening. While…

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Thanks largely to genomic advances, an increasing number of advocates are pushing for the use of genome sequencing to improve newborn screening. While this would undoubtedly improve risk assessment for a range of genetic conditions, challenges such as costs and ethical concerns could hinder rollout on a wider scale.

Newborn screening for potentially harmful diseases has existed in some form for around 60 years. Robert Guthrie is widely credited with introducing the first so-called ‘heel prick’ test for newborn babies to test for phenylketonuria (PKU), a serious metabolic condition that can be effectively cured by sticking to a specific diet.

Credit: Atiwat Studio / Getty Images

While the number of conditions screened for depends a lot on the country, region and hospital, the introduction of tandem mass spectroscopy helped allow this type of screening to expand to include more than 50 additional, mostly metabolic, conditions, saving 6800 lives a year in the U.S.

Since the human genome project was declared complete in 2003, genetic sequencing technology has changed out of all recognition. Rapid increases in speed and accuracy over the last two decades have occurred alongside dramatic cost reductions making mass sequencing projects such as the UK’s 100,000 Genomes Project, which began in 2013 and ended in 2018, a feasible reality.

Stephen KIngsmore
Stephen KIngsmore
CEO, Rady Children’s Institute

Sequencing technology is now also being applied to newborns both to diagnose unknown conditions and to screen healthy babies, albeit still in a research setting. Work done by Rady Children’s Institute for Genomic Medicine in California, led by its president and CEO Stephen Kingsmore, has done much to support sequencing for children with undiagnosed disorders over the last few years. “Thirty-one published studies have shown that genome sequencing of newborns with severe illnesses leads to diagnosis of underpinning genetic diseases in 36%, changes in how those babies are treated in 27%, and changes in outcomes in 18%,” Kingsmore told Inside Precision Medicine.

On the screening side, Robert C. Green, a professor at Harvard Medical School and medical geneticist at Brigham and Women’s Hospital, was ahead of the field when he set up the first BabySeq project in 2015 with co-director Alan Beggs to screen healthy newborns using exome sequencing. After the first phase was completed successfully, seven years down the line the second phase of the project is now underway.

In the U.K., Genomics England is in the first stages of an ambitious pilot project –the Newborn Genomes Programme. This project will start recruiting in 2023 and aims to sequence up to 200,000 healthy newborns to assess the feasibility of a larger roll out across the country’s National Health Service (NHS) in the future.

Despite these positive steps, a number of logistical, financial and ethical challenges remain before largescale genomic sequencing of newborns can be rolled out. The results of these ongoing studies, and the challenges they encounter, will help clarify when and how this type of screening will be adopted in countries around the world.

 

Rapid sequencing to target rare disease
According to Kingsmore, newborn diagnostic sequencing has the potential to diagnose over 7000 genetic diseases. “However, only about 400 genetic diseases are severe enough and have sufficiently effective treatments today that they should be screened in all newborns today,” he believes. Kingsmore and colleagues proved the validity of such sequencing through Project Baby Bear. Set up in California in 2018, the pilot project was the first state-funded program to use genome sequencing as a diagnostic method for critically ill newborns suspected of having a rare genetic disease.

Sequencing 178 critically ill babies over an 18-month period, the project diagnosed genetic conditions in 76 (43%) cases, 55 of whom were not previously receiving the correct care for their condition. Baby Bear is estimated to have saved $2.5 million in medical costs for the children involved.

Caleb Bupp
Caleb Bupp, MD
Michigan State University

Inspired by Project Baby Bear, Caleb Bupp, a clinical geneticist and assistant professor at Michigan State University, and colleagues have set up a sister project in Michigan, also named after their state animal.

“Project Baby Deer is a Michigan wide program…We’ve aimed it at having access for kids, regardless of where they’re born, or what hospital they may be admitted to, which I think was a little bit unique,” Bupp explained in an interview.

Set up in collaboration with Rady, who are managing the rapid sequencing pipeline for the project, Project Baby Deer began roll-out in 2020 and achieved Medicaid coverage in 2021. It includes 8 hospitals across the state and has already enrolled more than 80 children.

Some of the hospitals taking part in the program are smaller and less well resourced than others. Lack of in-depth genetics information or staff with expert knowledge can be a problem, according to Bupp, but he says the pandemic has actually helped solve this issue by boosting telehealth resources and familiarity in the region.

“We’ve worked out a fairly good telehealth system for being able to tap into expertise if we need to… I think that’s lowered some of the anxiety and the burden on some of the smaller centers so that they don’t have to feel like they have to figure this out 100% by themselves.”

 

Robert C. Green
Robert C. Green
Professor, Harvard Medical School

Newborn sequencing as a public health tool
One of the pioneers in newborn sequencing, Green had previously led several other sequencing projects in adults before getting funding for the first phase of the BabySeq trial in 2015.

The research team managed to recruit 324 babies and their families to take part in the first phase of BabySeq, 67 sick babies admitted to intensive care and 257 healthy babies. The infants were randomly assigned to receive a consultation about family history of genetic disorders only, or the same consultation plus exome sequencing.

The results showed that 11% of the babies sequenced carried dominant monogenic mutations linked to health, 88% had recessive carrier mutations that could impact their parents reproductive planning and 5% carried pharmacogenetic variants that could impact their response to childhood medications.

Green explained that he and his colleagues learnt a lot about how to run these kinds of trials during the study. “We basically went door-to-door to ask the families to participate. And what we found, unsurprisingly, was that immediately after you’ve had a baby, is not necessarily the best time to listen to a complicated pitch about how we’re going to stick your baby for some more blood, and randomize you into a complicated trial… So, it was a struggle to meet our original recruitment goals in that way.” This is just one takeaway that Green and colleagues used when putting together a proposal for the second phase of BabySeq, which has been funded by the NIH as an expansion to 500 families, but has not yet started recruiting.

“We have a stakeholder board now of community members, including individuals from BabySeq 1 who are advising us on better communication strategies. So, we’re bootstrapping, I think, a very much better approach to families,” Green explains.

“We’re also going to do this more in pediatric practices that have been selected for having diverse populations in three separate cities: Boston, New York City and Birmingham, Alabama.”

Sequencing technology has developed at such a pace that what was not possible, or at least difficult, in 2015 is now a reality. Genomics England recently helped launch the NHS Genomic Medicine Service in the U.K. While still in its infancy, according to its website, the new addition to the NHS aims to “be the first national health care system to offer whole genome sequencing as part of routine care.”

As part of the new service, Genomics England is planning an ambitious pilot project to sequence up to 200,000 newborn genomes to test the feasibility of this kind of screening in a research setting. After a public consultation last year that revealed a high level of support for the project, Genomics England plans to begin recruiting babies and their families to take part in the pilot from as early as Spring 2023.

Richard Scott,
Richard Scott
Consultant, Great Ormond Street Hospital

Richard Scott is a Consultant at Great Ormond Street Hospital for Children in London and also Chief Medical Officer at Genomics England. During an interview he explained some of the reasoning behind the new project. “We are at a point where currently the number of conditions that one can screen for in most countries is really quite narrow. And there’s obviously an enormous potential to think about a wider number of conditions that you might be able to screen for using genomics… I think there’s a real impetus to ask whether there are better ways of doing this alongside the heel prick test.”

The idea of running the project within the NHS means that the team running the study can assess how easy it would be to roll out this kind of testing to all newborns and also assess realistic costs and potential savings. The project will also feed data into rare disease research to help develop new therapeutics.

Another consideration that will be considered as part of the project is the potential for sequencing a child’s genome and keeping the data long term to refer back to if they become sick in later life.

“I think the future is definitely one where genomics is entirely embedded in healthcare,” says Scott. “It’s still an open question exactly how that will work. Sequencing technologies have changed a lot in the last 10 or 15 years and they are likely to change a lot again… At the moment, there’s a model to sequence once and go back and look at data whenever is needed, which we’ll be exploring through this programme. But it might also be that we actually store less data, but are able to answer the questions we need to by resequencing.”

 

Overcoming challenges
Before newborn sequencing can be rolled out on a larger scale, either for diagnostic or screening purposes, there are a number of challenges that need to be overcome.

Erica Ramos
Erica Ramos
VP, Genome Medical

One is ensuring everyone who needs sequencing for diagnostic purposes can get access to it. Erica Ramos is a genetic counsellor by training and current Vice President, Population Genomics at Genome Medical, a digital health company and specialty medical group.

“It is expensive to do rapid genome sequencing. Currently, it’s only available through these somewhat narrowly focused research efforts and in certain hospitals and health systems… so I think equitable access to that type of program by region is going to be an ongoing concern.”

Kingsmore and the Rady team have spent years setting up a fast and efficient sequencing pipeline, but this is not an easy thing to set up overnight. “Rapid genome sequencing is not the same ballgame as whole genome sequencing, to be able to have the workflows and all of the tools and technologies that enable that fast evaluation and confident evaluation takes a big team and a long time to develop,” explains Ramos.

Euan Ashley
Euan Ashley
Clincal Geneticist, Stanford Professor

Stanmore professor and clinical geneticist Euan Ashley and his team recently hit the news with a new world record for sequencing a genome in just over 5 hours and completing a genetic diagnosis for a patient in under 8 hours. He says that the type of sequencing machine used can make a difference to how affordable and accessible this type of service can be.

Their record used Oxford Nanopore’s PromethION 48 sequencer. While their reasoning for using this machine, rather than the more common Illumina machines found in most hospital laboratories, was its speed and long-read sequencing ability, Ashley says the different approach could actually be a more affordable option for smaller centers.

“With some sequencing machines, your hospital or the healthcare system has to come up with half a million dollars or more just to buy the machine. The way Oxford Nanopore operates is you pay for the flow cells, but you don’t really pay for the machine. Getting hold of one of the machines comes down to whether you are going to order enough flow cells.” he explained.

Simply sequencing faster can also save money, particularly if the patient is critically ill. “There is a big difference between eight hours and 24–48 hours,” says Ashley. “For these patients it could be life and death. It’s also money, because it’s $15,000 a day to stay in a critical care unit. And that could be even higher, depending on the support you have.”

Jeanette McCarthy
Jeanette McCarthy, Fabric Genomics

Another potential problem for smaller centers wanting to rollout newborn sequencing programs is that the advanced genetics expertise needed for sequence analysis can be lacking. This is something that Fabric Genomics is tackling with its artificial intelligence (AI) driven genome analysis tools, which are already being used by Kingsmore’s team at Rady. “They use our AI algorithm, which is called GEM. And that does a very good job at very quickly distilling an entire genome down into a very small number of candidates to look at,” explained Jeanette McCarthy, VP of Precision Medicine at Fabric. But she adds that the company also helps centers with less available expertise. “We offer a whole package from when the data comes off the sequencer through generating a physician ready clinical report. A laboratory might purchase our software, but then they can’t find anybody to hire to analyze it. There’s a limited pool of genetics experts that can handle the whole genome sequence data analysis, so we offer those services to our customers.”

In terms of newborn screening in healthy babies, a big point of current debate is what findings should be returned to parents about their children. While many err on the side of returning only ‘medically actionable’ findings, in other words, genetic variants linked to diseases that are treatable and start in childhood, there are others who think a greater range of information could be shared.

“If you tell a parent that their infant is carrying a mutation for something that could eventually be deadly, that’s pretty scary. But we have now done this in several hundred infants, found such mutations and told their parents. We demonstrated that these parents are resilient and understand and want that information,” emphasizes Green.

“We never want to be cavalier about the potential for distress. But the narrative of widespread catastrophic distress in the face of genetic risk information is simply not true.”

DNA fetus
Credit: Rasi Bhadramani / Getty Images

 

A future of genetic medicine
We may still be a few years off from a future where everyone has their genome sequenced and accessible in their medical records in case of future need, but the experts seem to agree that we are moving slowly in this direction.

Sequencing newborns to help treat undiagnosed conditions is growing in acceptance and is, arguably, the first step on the road to wider rollout of early sequencing for screening purposes.

One thing that is hard to predict is how far genomic technology, and indeed technology in general, will have advanced in 10-20 years. At the moment storing even one genome takes a lot of computing power and the chance of being able to access genomic data easily, such as through electronic health records, seems remote. However, technology changes quickly and it’s possible that there is a breakthrough that will allow this just around the corner.

From the consultations carried out by both the BabySeq and Genomics England researchers there seems to be demand from the public for sequencing-based newborn screening. There is still debate among experts as to what findings should be returned to parents and their children, but most are advocating for the sharing of information on childhood onset diseases that are currently treatable, at least as a first step.

David Bick
David Bick
Medical Geneticist, Genomics England

“After we’ve done this for 5 or 10 years, people may feel differently, because the general populations attitude toward technology changes over time,” says David Bick, an experienced medical geneticist and clinical advisor for Genomics England on the newborn sequencing project.

“There’s just so many different what ifs that I think it’s really important that we continue to have these conversations about what the ethics and morals of these activities are, and also how they apply in different scenarios. Not just in the early adopter, wealthy, White, employed and English-speaking population that has really led a lot of these types of efforts so far,” adds Ramos.

The post The Changing Face of Newborn Screening appeared first on Inside Precision Medicine.

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Congress’ failure so far to deliver on promise of tens of billions in new research spending threatens America’s long-term economic competitiveness

A deal that avoided a shutdown also slashed spending for the National Science Foundation, putting it billions below a congressional target intended to…

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Science is again on the chopping block on Capitol Hill. AP Photo/Sait Serkan Gurbuz

Federal spending on fundamental scientific research is pivotal to America’s long-term economic competitiveness and growth. But less than two years after agreeing the U.S. needed to invest tens of billions of dollars more in basic research than it had been, Congress is already seriously scaling back its plans.

A package of funding bills recently passed by Congress and signed by President Joe Biden on March 9, 2024, cuts the current fiscal year budget for the National Science Foundation, America’s premier basic science research agency, by over 8% relative to last year. That puts the NSF’s current allocation US$6.6 billion below targets Congress set in 2022.

And the president’s budget blueprint for the next fiscal year, released on March 11, doesn’t look much better. Even assuming his request for the NSF is fully funded, it would still, based on my calculations, leave the agency a total of $15 billion behind the plan Congress laid out to help the U.S. keep up with countries such as China that are rapidly increasing their science budgets.

I am a sociologist who studies how research universities contribute to the public good. I’m also the executive director of the Institute for Research on Innovation and Science, a national university consortium whose members share data that helps us understand, explain and work to amplify those benefits.

Our data shows how underfunding basic research, especially in high-priority areas, poses a real threat to the United States’ role as a leader in critical technology areas, forestalls innovation and makes it harder to recruit the skilled workers that high-tech companies need to succeed.

A promised investment

Less than two years ago, in August 2022, university researchers like me had reason to celebrate.

Congress had just passed the bipartisan CHIPS and Science Act. The science part of the law promised one of the biggest federal investments in the National Science Foundation in its 74-year history.

The CHIPS act authorized US$81 billion for the agency, promised to double its budget by 2027 and directed it to “address societal, national, and geostrategic challenges for the benefit of all Americans” by investing in research.

But there was one very big snag. The money still has to be appropriated by Congress every year. Lawmakers haven’t been good at doing that recently. As lawmakers struggle to keep the lights on, fundamental research is quickly becoming a casualty of political dysfunction.

Research’s critical impact

That’s bad because fundamental research matters in more ways than you might expect.

For instance, the basic discoveries that made the COVID-19 vaccine possible stretch back to the early 1960s. Such research investments contribute to the health, wealth and well-being of society, support jobs and regional economies and are vital to the U.S. economy and national security.

Lagging research investment will hurt U.S. leadership in critical technologies such as artificial intelligence, advanced communications, clean energy and biotechnology. Less support means less new research work gets done, fewer new researchers are trained and important new discoveries are made elsewhere.

But disrupting federal research funding also directly affects people’s jobs, lives and the economy.

Businesses nationwide thrive by selling the goods and services – everything from pipettes and biological specimens to notebooks and plane tickets – that are necessary for research. Those vendors include high-tech startups, manufacturers, contractors and even Main Street businesses like your local hardware store. They employ your neighbors and friends and contribute to the economic health of your hometown and the nation.

Nearly a third of the $10 billion in federal research funds that 26 of the universities in our consortium used in 2022 directly supported U.S. employers, including:

  • A Detroit welding shop that sells gases many labs use in experiments funded by the National Institutes of Health, National Science Foundation, Department of Defense and Department of Energy.

  • A Dallas-based construction company that is building an advanced vaccine and drug development facility paid for by the Department of Health and Human Services.

  • More than a dozen Utah businesses, including surveyors, engineers and construction and trucking companies, working on a Department of Energy project to develop breakthroughs in geothermal energy.

When Congress shortchanges basic research, it also damages businesses like these and people you might not usually associate with academic science and engineering. Construction and manufacturing companies earn more than $2 billion each year from federally funded research done by our consortium’s members.

A lag or cut in federal research funding would harm U.S. competitiveness in critical advanced technologies such as artificial intelligence and robotics. Hispanolistic/E+ via Getty Images

Jobs and innovation

Disrupting or decreasing research funding also slows the flow of STEM – science, technology, engineering and math – talent from universities to American businesses. Highly trained people are essential to corporate innovation and to U.S. leadership in key fields, such as AI, where companies depend on hiring to secure research expertise.

In 2022, federal research grants paid wages for about 122,500 people at universities that shared data with my institute. More than half of them were students or trainees. Our data shows that they go on to many types of jobs but are particularly important for leading tech companies such as Google, Amazon, Apple, Facebook and Intel.

That same data lets me estimate that over 300,000 people who worked at U.S. universities in 2022 were paid by federal research funds. Threats to federal research investments put academic jobs at risk. They also hurt private sector innovation because even the most successful companies need to hire people with expert research skills. Most people learn those skills by working on university research projects, and most of those projects are federally funded.

High stakes

If Congress doesn’t move to fund fundamental science research to meet CHIPS and Science Act targets – and make up for the $11.6 billion it’s already behind schedule – the long-term consequences for American competitiveness could be serious.

Over time, companies would see fewer skilled job candidates, and academic and corporate researchers would produce fewer discoveries. Fewer high-tech startups would mean slower economic growth. America would become less competitive in the age of AI. This would turn one of the fears that led lawmakers to pass the CHIPS and Science Act into a reality.

Ultimately, it’s up to lawmakers to decide whether to fulfill their promise to invest more in the research that supports jobs across the economy and in American innovation, competitiveness and economic growth. So far, that promise is looking pretty fragile.

This is an updated version of an article originally published on Jan. 16, 2024.

Jason Owen-Smith receives research support from the National Science Foundation, the National Institutes of Health, the Alfred P. Sloan Foundation and Wellcome Leap.

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What’s Driving Industrial Development in the Southwest U.S.

The post-COVID-19 pandemic pipeline, supply imbalances, investment and construction challenges: these are just a few of the topics address by a powerhouse…

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The post-COVID-19 pandemic pipeline, supply imbalances, investment and construction challenges: these are just a few of the topics address by a powerhouse panel of executives in industrial real estate this week at NAIOP’s I.CON West in Long Beach, California. Led by Dawn McCombs, principal and Denver lead industrial specialist for Avison Young, the panel tackled some of the biggest issues facing the sector in the Western U.S. 

Starting with the pandemic in 2020 and continuing through 2022, McCombs said, the industrial sector experienced a huge surge in demand, resulting in historic vacancies, rent growth and record deliveries. Operating fundamentals began to normalize in 2023 and construction starts declined, certainly impacting vacancy and absorption moving forward.  

“Development starts dropped by 65% year-over-year across the U.S. last year. In Q4, we were down 25% from pre-COVID norms,” began Megan Creecy-Herman, president, U.S. West Region, Prologis, noting that all of that is setting us up to see an improvement of fundamentals in the market. “U.S. vacancy ended 2023 at about 5%, which is very healthy.” 

Vacancies are expected to grow in Q1 and Q2, peaking mid-year at around 7%. Creecy-Herman expects to see an increase in absorption as customers begin to have confidence in the economy, and everyone gets some certainty on what the Fed does with interest rates. 

“It’s an interesting dynamic to see such a great increase in rents, which have almost doubled in some markets,” said Reon Roski, CEO, Majestic Realty Co. “It’s healthy to see a slowing down… before [rents] go back up.” 

Pre-pandemic, a lot of markets were used to 4-5% vacancy, said Brooke Birtcher Gustafson, fifth-generation president of Birtcher Development. “Everyone was a little tepid about where things are headed with a mediocre outlook for 2024, but much of this is normalizing in the Southwest markets.”  

McCombs asked the panel where their companies found themselves in the construction pipeline when the Fed raised rates in 2022.   

In Salt Lake City, said Angela Eldredge, chief operations officer at Price Real Estate, there is a typical 12-18-month lead time on construction materials. “As rates started to rise in 2022, lots of permits had already been pulled and construction starts were beginning, so those project deliveries were in fall 2023. [The slowdown] was good for our market because it kept rates high, vacancies lower and helped normalize the market to a healthy pace.” 

A supply imbalance can stress any market, and Gustafson joked that the current imbalance reminded her of a favorite quote from the movie Super Troopers: “Desperation is a stinky cologne.” “We’re all still a little crazed where this imbalance has put us, but for the patient investor and owner, there will be a rebalancing and opportunity for the good quality real estate to pass the sniff test,” she said.  

At Bircher, Gustafson said that mid-pandemic, there were predictions that one billion square feet of new product would be required to meet tenant demand, e-commerce growth and safety stock. That transition opened a great opportunity for investors to run at the goal. “In California, the entitlement process is lengthy, around 24-36 months to get from the start of an acquisition to the completion of a building,” she said. Fast forward to 2023-2024, a lot of what is being delivered in 2024 is the result of that chase.  

“Being an optimistic developer, there is good news. The supply imbalance helped normalize what was an unsustainable surge in rents and land values,” she said. “It allowed corporate heads of real estate to proactively evaluate growth opportunities, opened the door for contrarian investors to land bank as values drop, and provided tenants with options as there is more product. Investment goals and strategies have shifted, and that’s created opportunity for buyers.” 

“Developers only know how to run and develop as much as we can,” said Roski. “There are certain times in cycles that we are forced to slow down, which is a good thing. In the last few years, Majestic has delivered 12-14 million square feet, and this year we are developing 6-8 million square feet. It’s all part of the cycle.”  

Creecy-Herman noted that compared to the other asset classes and opportunities out there, including office and multifamily, industrial remains much more attractive for investment. “That was absolutely one of the things that underpinned the amount of investment we saw in a relatively short time period,” she said.  

Market rent growth across Los Angeles, Inland Empire and Orange County moved up more than 100% in a 24-month period. That created opportunities for landlords to flexible as they’re filling up their buildings. “Normalizing can be uncomfortable especially after that kind of historic high, but at the same time it’s setting us up for strong years ahead,” she said. 

Issues that owners and landlords are facing with not as much movement in the market is driving a change in strategy, noted Gustafson. “Comps are all over the place,” she said. “You have to dive deep into every single deal that is done to understand it and how investment strategies are changing.” 

Tenants experienced a variety of challenges in the pandemic years, from supply chain to labor shortages on the negative side, to increased demand for products on the positive, McCombs noted.  

“Prologis has about 6,700 customers around the world, from small to large, and the universal lesson [from the pandemic] is taking a more conservative posture on inventories,” Creecy-Herman said. “Customers are beefing up inventories, and that conservatism in the supply chain is a lesson learned that’s going to stick with us for a long time.” She noted that the company has plenty of clients who want to take more space but are waiting on more certainty from the broader economy.  

“E-commerce grew by 8% last year, and we think that’s going to accelerate to 10% this year. This is still less than 25% of all retail sales, so the acceleration we’re going to see in e-commerce… is going to drive the business forward for a long time,” she said. 

Roski noted that customers continually re-evaluate their warehouse locations, expanding during the pandemic and now consolidating but staying within one delivery day of vast consumer bases.  

“This is a generational change,” said Creecy-Herman. “Millions of young consumers have one-day delivery as a baseline for their shopping experience. Think of what this means for our business long term to help our customers meet these expectations.” 

McCombs asked the panelists what kind of leasing activity they are experiencing as a return to normalcy is expected in 2024. 

“During the pandemic, shifts in the ports and supply chain created a build up along the Mexican border,” said Roski, noting border towns’ importance to increased manufacturing in Mexico. A shift of populations out of California and into Arizona, Nevada, Texas and Florida have resulted in an expansion of warehouses in those markets. 

Eldridge said that Salt Lake City’s “sweet spot” is 100-200 million square feet, noting that the market is best described as a mid-box distribution hub that is close to California and Midwest markets. “Our location opens up the entire U.S. to our market, and it’s continuing to grow,” she said.   

The recent supply chain and West Coast port clogs prompted significant investment in nearshoring and port improvements. “Ports are always changing,” said Roski, listing a looming strike at East Coast ports, challenges with pirates in the Suez Canal, and water issues in the Panama Canal. “Companies used to fix on one port and that’s where they’d bring in their imports, but now see they need to be [bring product] in a couple of places.” 

“Laredo, [Texas,] is one of the largest ports in the U.S., and there’s no water. It’s trucks coming across the border. Companies have learned to be nimble and not focused on one area,” she said. 

“All of the markets in the southwest are becoming more interconnected and interdependent than they were previously,” Creecy-Herman said. “In Southern California, there are 10 markets within 500 miles with over 25 million consumers who spend, on average, 10% more than typical U.S. consumers.” Combined with the port complex, those fundamentals aren’t changing. Creecy-Herman noted that it’s less of a California exodus than it is a complementary strategy where customers are taking space in other markets as they grow. In the last 10 years, she noted there has been significant maturation of markets such as Las Vegas and Phoenix. As they’ve become more diversified, customers want to have a presence there. 

In the last decade, Gustafson said, the consumer base has shifted. Tenants continue to change strategies to adapt, such as hub-and-spoke approaches.  From an investment perspective, she said that strategies change weekly in response to market dynamics that are unprecedented.  

McCombs said that construction challenges and utility constraints have been compounded by increased demand for water and power. 

“Those are big issues from the beginning when we’re deciding on whether to buy the dirt, and another decision during construction,” Roski said. “In some markets, we order transformers more than a year before they are needed. Otherwise, the time comes [to use them] and we can’t get them. It’s a new dynamic of how leases are structured because it’s something that’s out of our control.” She noted that it’s becoming a bigger issue with electrification of cars, trucks and real estate, and the U.S. power grid is not prepared to handle it.  

Salt Lake City’s land constraints play a role in site selection, said Eldridge. “Land values of areas near water are skyrocketing.” 

The panelists agreed that a favorable outlook is ahead for 2024, and today’s rebalancing will drive a healthy industry in the future as demand and rates return to normalized levels, creating opportunities for investors, developers and tenants.  


This post is brought to you by JLL, the social media and conference blog sponsor of NAIOP’s I.CON West 2024. Learn more about JLL at www.us.jll.com or www.jll.ca.

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Analyst reviews Apple stock price target amid challenges

Here’s what could happen to Apple shares next.

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They said it was bound to happen.

It was Jan. 11, 2024 when software giant Microsoft  (MSFT)  briefly passed Apple  (AAPL)  as the most valuable company in the world.

Microsoft's stock closed 0.5% higher, giving it a market valuation of $2.859 trillion. 

It rose as much as 2% during the session and the company was briefly worth $2.903 trillion. Apple closed 0.3% lower, giving the company a market capitalization of $2.886 trillion. 

"It was inevitable that Microsoft would overtake Apple since Microsoft is growing faster and has more to benefit from the generative AI revolution," D.A. Davidson analyst Gil Luria said at the time, according to Reuters.

The two tech titans have jostled for top spot over the years and Microsoft was ahead at last check, with a market cap of $3.085 trillion, compared with Apple's value of $2.684 trillion.

Analysts noted that Apple had been dealing with weakening demand, including for the iPhone, the company’s main source of revenue. 

Demand in China, a major market, has slumped as the country's economy makes a slow recovery from the pandemic and competition from Huawei.

Sales in China of Apple's iPhone fell by 24% in the first six weeks of 2024 compared with a year earlier, according to research firm Counterpoint, as the company contended with stiff competition from a resurgent Huawei "while getting squeezed in the middle on aggressive pricing from the likes of OPPO, vivo and Xiaomi," said senior Analyst Mengmeng Zhang.

“Although the iPhone 15 is a great device, it has no significant upgrades from the previous version, so consumers feel fine holding on to the older-generation iPhones for now," he said.

A man scrolling through Netflix on an Apple iPad Pro. Photo by Phil Barker/Future Publishing via Getty Images.

Future Publishing/Getty Images

Big plans for China

Counterpoint said that the first six weeks of 2023 saw abnormally high numbers with significant unit sales being deferred from December 2022 due to production issues.

Apple is planning to open its eighth store in Shanghai – and its 47th across China – on March 21.

Related: Tech News Now: OpenAI says Musk contract 'never existed', Xiaomi's EV, and more

The company also plans to expand its research centre in Shanghai to support all of its product lines and open a new lab in southern tech hub Shenzhen later this year, according to the South China Morning Post.

Meanwhile, over in Europe, Apple announced changes to comply with the European Union's Digital Markets Act (DMA), which went into effect last week, Reuters reported on March 12.

Beginning this spring, software developers operating in Europe will be able to distribute apps to EU customers directly from their own websites instead of through the App Store.

"To reflect the DMA’s changes, users in the EU can install apps from alternative app marketplaces in iOS 17.4 and later," Apple said on its website, referring to the software platform that runs iPhones and iPads. 

"Users will be able to download an alternative marketplace app from the marketplace developer’s website," the company said.

Apple has also said it will appeal a $2 billion EU antitrust fine for thwarting competition from Spotify  (SPOT)  and other music streaming rivals via restrictions on the App Store.

The company's shares have suffered amid all this upheaval, but some analysts still see good things in Apple's future.

Bank of America Securities confirmed its positive stance on Apple, maintaining a buy rating with a steady price target of $225, according to Investing.com

The firm's analysis highlighted Apple's pricing strategy evolution since the introduction of the first iPhone in 2007, with initial prices set at $499 for the 4GB model and $599 for the 8GB model.

BofA said that Apple has consistently launched new iPhone models, including the Pro/Pro Max versions, to target the premium market. 

Analyst says Apple selloff 'overdone'

Concurrently, prices for previous models are typically reduced by about $100 with each new release. 

This strategy, coupled with installment plans from Apple and carriers, has contributed to the iPhone's installed base reaching a record 1.2 billion in 2023, the firm said.

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Apple has effectively shifted its sales mix toward higher-value units despite experiencing slower unit sales, BofA said.

This trend is expected to persist and could help mitigate potential unit sales weaknesses, particularly in China. 

BofA also noted Apple's dominance in the high-end market, maintaining a market share of over 90% in the $1,000 and above price band for the past three years.

The firm also cited the anticipation of a multi-year iPhone cycle propelled by next-generation AI technology, robust services growth, and the potential for margin expansion.

On Monday, Evercore ISI analysts said they believed that the sell-off in the iPhone maker’s shares may be “overdone.”

The firm said that investors' growing preference for AI-focused stocks like Nvidia  (NVDA)  has led to a reallocation of funds away from Apple. 

In addition, Evercore said concerns over weakening demand in China, where Apple may be losing market share in the smartphone segment, have affected investor sentiment.

And then ongoing regulatory issues continue to have an impact on investor confidence in the world's second-biggest company.

“We think the sell-off is rather overdone, while we suspect there is strong valuation support at current levels to down 10%, there are three distinct drivers that could unlock upside on the stock from here – a) Cap allocation, b) AI inferencing, and c) Risk-off/defensive shift," the firm said in a research note.

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