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New diagnostic tool achieves accuracy of PCR tests with faster and simpler nanopore system

Over the past four years, many of us have become accustomed to a swab up the nose to test for COVID-19, using at-home rapid antigen tests or the more accurate…

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Over the past four years, many of us have become accustomed to a swab up the nose to test for COVID-19, using at-home rapid antigen tests or the more accurate clinic-provided PCR tests with a longer processing time. Now a new diagnostic tool developed by UC Santa Cruz Distinguished Professor of Electrical and Computer Engineering Holger Schmidt and his collaborators can test for SARS-CoV-2 and Zika virus with the same or better accuracy as high-precision PCR tests in a matter of hours.

Credit: Mohammad Julker Neyen Sampad, UC Santa Cruz

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Over the past four years, many of us have become accustomed to a swab up the nose to test for COVID-19, using at-home rapid antigen tests or the more accurate clinic-provided PCR tests with a longer processing time. Now a new diagnostic tool developed by UC Santa Cruz Distinguished Professor of Electrical and Computer Engineering Holger Schmidt and his collaborators can test for SARS-CoV-2 and Zika virus with the same or better accuracy as high-precision PCR tests in a matter of hours.

In a new paper in the journal Proceedings of the National Academy of Sciences, Schmidt and the project team describe their system, which combines optofluidics and nanopore technology to create a lab-on-a-chip diagnostic system. The team’s success with animal models makes them hopeful that this technology could be a major innovation for the future of rapid diagnostics. 

“This could turn into the next big diagnostic system,” said Aaron Hawkins, a professor of Electrical and Computer Engineering at Brigham Young University and a senior author on the paper. “You get sick, you go to the hospital or doctor, and their tests rely on this technology. There’s a path where this could be installed right there [in a hospital or clinic], so you wouldn’t have to wait to get your results.”

This research is a result of longstanding collaboration between Schmidt, Hawkins, and Professor Jean Patterson at the Texas Biomedical Research Institute. 

Faster and more accurate tests

While PCR testing is currently the gold standard of accuracy for virology testing, the method falls short in several ways. PCR tests are highly complex and require chemical reactions that must be performed by skilled operators, typically at a central laboratory, sometimes taking days to get testing results back. These complex reactions are needed for the amplification of viral DNA or RNA, a process of making multiple copies of the genetic material that can introduce and amplify error. 

PCR tests can also only detect nucleic acids, the material that makes up DNA and RNA. But in the case of some diseases, it can be incredibly useful to detect other biomarkers such as proteins.

The new diagnostic tool solves both of these problems. It requires little sample preparation and is completely amplification-free and label-free, the latter meaning it does not use light to identify biomarkers. This dramatically cuts down the time and complexity of the diagnosis process.

“The potential is enormous,” Patterson said. “The idea that you don’t have to amplify to get accurate results is a huge advance, on par with how PCR was an incredible step forward when it came out.”

Diagnostics design

The new diagnostic system combines Schmidt’s area of expertise in optofluidics, which is the control of tiny amounts of fluids with beams of light, with a nanopore for counting single nucleic acids to read genetic material. The tool was designed to test for Zika and COVID-19 viruses, which have been particularly medically relevant in recent years and priority areas for the National Institutes of Health, which funded this research. 

“We built up a simple lab-on-a-chip system that can perform testing at a miniature level with the help of microfluidics, silicon chips, and nanopore detection technologies,” said Mohammad Julker Neyen Sampad, Schmidt’s graduate student and the paper’s first author. “Simple, easy, low resource tool development was our goal — and I believe we got there.” 

To run the test, a sample of biofluid is mixed in a container with magnetic microbeads. For this study, the researchers used biofluids including saliva and blood from baboons and marmosets at Texas Biomedical Research Institute.

The microbeads are designed with a matching RNA sequence of the disease for which the test is designed to detect. For example, if it’s a COVID-19 detection test, the microbeads will have strands of SARS-CoV-2 RNA on them. If there is SARS-CoV-2 virus present in the sample, the virus’s RNA will bind to the beads. After a brief waiting period, the researcher pulls the magnetic beads down to the bottom of the container and washes everything else out. 

The beads are put into a silicon microfluidics chip designed and fabricated by Hawkins’ group, where they flow through a long, thin channel covered by an ultra-thin membrane, the design of which Hawkins calls an “engineering miracle.” The beads get caught in a light beam that pushes them against a wall in the channel, which contains a nanopore, a tiny opening just 20 nanometers across — for comparison, a human hair is about 80,000 – 100,000 nanometers wide.   

The researchers apply heat to the chip, which makes the RNA particles come off the beads and get sucked into the nanopore, which detects that the virus RNA is present.

Promising results

Their trials showed that the test correctly detected the virus for each sample that the PCR test was able to detect, even at extremely low concentrations of the virus. There were instances in which the PCR test was not able to detect a case of one of the viruses while Schmidt’s system did, showing their system can be more accurate than PCR.

Overall, the microfluidics system is much smaller and less complex than a PCR machine. If this concept is brought to market as a product, its compact size could easily fit in a researcher’s lab, enabling much faster results for virology testing, increasing testing accessibility and speeding up the time to results from days to hours.

“If we build an instrument out of this system, a researcher could have that in the biosafety level-4 lab where it never leaves the room, and you can just drop in a little sample liquid, and run the test in an hour,” Schmidt said. “I think that would help speed up the testing.”

The test was run with six different biofluids, including saliva, blood, and throat swabs, which may contain different viral loads. This can enable researchers to better study how diseases pass through the body of different animals. 

While at the current stage the test was developed to detect SARS-CoV-2 and Zika viruses, researchers could make adjustments to find any virus for which they have a genetic sample. In future developments, they plan for further simplification and minimization of the system, as well as enabling it to test for multiple types of disease at once, a feature called disease multiplexing. 

Schmidt also intends to use this concept to develop diagnostic tools for cancer biomarkers and other health conditions that leave traces of DNA/RNA or protein in the body. It will likely be a few years before this concept is commercialized and brought to market. 


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These National Parks are the most expensive to visit

A new report looks at the cost of entry fees at the country’s national parks.

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While the 63 national parks spread across the U.S. are an inextricable part of American culture, visiting all of them is by no means a cheap endeavor.

Many are not easy to access without a car and, along with the usual travel and accommodation costs of going to so many states and territories, the parks themselves also charge visitors fees at different points in their visit. Sometimes this is exclusively for “extras” such a spot on a camping site but, increasingly, parks have been either raising or introducing entry and parking fees amid overcrowding.

Related: I visited two of the country's most underrated National Parks — here's what it was like

The most expensive national park in the U.S. is, as travel journalist Stephen Hanson recently identified in a fare comparison, the Gates Of The Arctic National Park & Preserve in Northern Alaska.

Veronika Bondarenko captured this view at the New River Gorge National Park in West Virginia.

Veronika Bondarenko

This is the most remote (and often most expensive) national park to visit

Often dubbed the “most remote national park in the U.S.,” the Gates of the Arctic has no entry fee but is incredibly costly to get to due to its location in the far north of the Arctic. Without direct road access, the only way to get there is to fly from Anchorage to the nearest small settlement such as Kotzebue or Anaktuvuk Pass by charter plane. The Arctic terrain also means visitors often need to hire guides, pay inflated prices for the limited accommodation and bring special gear.

More Travel:

“While many beautiful national parks in the US are well worth a trip despite their remote setting, Gates of the Arctic National Park & Preserve requires a particularly dedicated resolve from any traveler who wants to visit,” Hanson writes. “Though prices can vary depending on the length of the trip and the destination, passengers can expect to pay anywhere from a few hundred to a few thousand dollars for a ticket.” 

Channel Islands National Park off the coast of Southern California is the country’s second-most expensive in the U.S. for a similar reason. The five Channel Islands sit in the Pacific Ocean and can only be accessed by ferry from Ventura Harbor. Depending on the time of day and year, the three-hour ferry ranges in price from $60 to $120 (the park itself, once you get there, has no entry fee.)

These national parks are also very expensive (here is why)

Parks that are easily accessible by car but have high entry fees due to overcrowding include Yosemite in California’s Sierra Nevada Mountains and Glacier National Park on the border between Montana and Canada’s British Columbia. 

Both parks charge each vehicle coming in a $35 entry fee on top of additional additional fees for staying there overnight. In 2021, Yosemite raised the camping fee from $6 to $10 per person to keep up with the cost of running the park amid growing numbers of people who started visiting as part of their local travels during the pandemic.

“Visitors should be prepared to spend more money on gas and set aside an entire day for travel when heading out to the park,” Hanson writes of Glacier National Park. “Upon arriving, visitors to Glacier will have to pay a $35 entry fee.”

SEE THE FULL LIST OF MOST EXPENSIVE NATIONAL PARKS HERE.

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Spread & Containment

Tackling social isolation could be more effective than healthy eating for obesity

A recent study showed encouraging people with obesity to interact with others more can keep them alive for longer.

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People with obesity are commonly urged to lose weight by eating more healthily, cutting down on calorie intake and exercising more – but that advice overlooks a crucial problem.

It overstates individual agency – putting the person at fault because of poor lifestyle choices – and doesn’t take into account all the factors contributing to the obesity crisis. For instance, research has found that there are significant social determinants of obesity, such as poverty, stigma and loneliness.

A recent study of people in the UK has suggested that one way to keep obese people alive for longer is to encourage them to interact more with other people.

Why exactly might this be?

The study came to its conclusion using something called hazard ratios, a measure of how often a particular event happens in one group compared to how often it happens in another group, over time. It found that people who’re less socially isolated have a reduced hazard ratio of death from any cause (known as all-cause mortality). This means that people who’re more socially connected are less likely to die prematurely from any cause.

This is even more significant in people with obesity. Isolation has a bigger affect on the risk of death in people with obesity than those at a healthy weight. Those with obesity showed a four times greater reduction in mortality risk than people without obesity when their levels of social isolation fell.

We also know obesity leads to a higher risk of social isolation, which in turn has mental and physical health implications. So it’s not surprising that reducing social isolation amongst among people who are obese would reduce the risk of mortality.

However, the degree of change is perhaps unexpected. It means that tackling social isolation could make a bigger difference to those with obesity than other contributing factors. In fact, the study found a reduction in social isolation more associated with decreased risk of death than any other factor, including a healthy diet, physical activity, alcohol consumption, depression and anxiety.

Relationship between social isolation and obesity

Obesity is a medical condition where people have excessive body fat, as measured by their body mass index. Growing rates of obesity means some studies predict around 20% of the global adult population will be obese by 2030.

And the problem is worse in high income countries. Around 25% of adults in the UK are already considered obese, and the rate in the US could become as high as 45% by 2035.

This rise is intertwined with growing levels of social isolation and loneliness. Both increased during the COVID pandemic and and both are linked with a greater risk of mortality, just like obesity.

There is a two-way relationship between obesity and social isolation. In an attempt to escape feelings of isolation, people may consume more food and drink than usual, or eat more unhealthy foods such as chocolate, cake, biscuits – so called comfort foods.

Being isolated and feeling lonely can also lead to a reduction in exercise. Both excessive eating of unhealthy food and a lack of exercise will inevitably lead to weight gain.

On the other hand, obesity can lead to social isolation and loneliness, as people experience stigmatisation, rejection, discrimination, bullying, self-blame and reduced self-esteem. It can also engender a loss of trust in others, and a perception that social situations pose a threat, so are best avoided.

We also know obesity is associated with poorer mental health, especially in women.

Unsurprisingly then, obese people are more likely to isolate themselves, avoid spending time in public places and interacting with others. This can include an avoidance of health care settings, preventing those struggling with weight gain from getting the necessary support.

The most recent study demonstrates the significant damage that social isolation can have on those with obesity. The findings should not be interpreted as a signal that the sole answer to health risks of obesity is making social connections. However, the study should prompt a rethink of attitudes and approaches to obesity that focus exclusively on the individual’s diet and exercise. Research has shown that the traditional “eat less, move more” advice is simplistic and outdated.

Healthy eating and exercise should not be prioritised in obesity treatment at the expense of all other factors. To reduce the mortality risk of obesity, social isolation must be taken into account alongside healthy eating and physical activities. Tackling obesity, then, should include group activities and opportunities for regular social interaction in safe welcoming environments.

Andrea Wigfield does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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Spread & Containment

A dramatic schism over social issues? The United Methodist Church has been here before – but this time, America’s religious landscape is far different

The United Methodist Church will hold its General Conference, delayed several years by the pandemic, in April 2024. The meeting comes amid a dramatic divide…

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Debates over LGBTQ+ issues have divided Methodist congregations for years leading up to the current schism. AP Photo/Charlie Riedel, File

The United Methodist Church’s General Conference will meet in Charlotte, North Carolina from April 23 to May 4, 2024. Originally scheduled for 2020 and delayed three times due to the COVID-19 pandemic, this meeting of the church’s legislative body comes at a critical time for the United States’ second-largest Protestant denomination.

In 2022, conservative Methodists announced a break with the UMC, forming the Global Methodist Church. These leaders believed that the UMC had become too liberal, drifting away from orthodoxy. The issue at the heart of the split, however, revolves around the UMC’s long-standing battle over LGBTQ+ rights.

This denominational split draws comparisons to one in 1844, when Methodists divided over slavery. As a scholar of American religious history and Methodist studies, I see parallels but also great differences between the current schism and the one in 1844.

Both schisms center on predominant social issues of their eras. The current schism, however, comes at a time when United Methodists, like other American churches, must navigate a changing religious landscape – one where church membership is declining, especially among younger Americans.

Methodist roots

The UMC traces its origins to the 18th-century Anglican clergyman John Wesley, who sought to reinvigorate Anglicans’ sense of personal faith.

Emphasizing piety and social engagement, Wesley’s followers spread Methodism throughout the British Isles and North America. As the movement grew, his followers separated from the Anglican Church to form several Methodist denominations.

The upper half of a statue of a man with wavy hair in a heavy coat.
A statue of John Wesley sculpted by Paul Raphael Montford, in Melbourne, Australia. Adam Carr/Wikimedia Commons

The first Methodist church in the U.S., the Methodist Episcopal Church, was founded in 1784. This church and smaller Methodist denominations grew rapidly. By 1850, approximately 1 in 3 Americans affiliated with a church was a Methodist.

Today, there are 80 Methodist and Wesleyan denominations around the world, with the UMC being the largest.

The 1844 rupture

Like other Protestant churches before the Civil War, Methodists were divided over slavery.

Wesley viewed slavery as a great social evil that deprived enslaved people of God-given human rights. However, U.S. Methodists – including one of the founders of the Methodist Episcopal Church, Francis Asbury – worried that enforcing the church’s prohibitions against slavery would alienate members in the South. For much of the early 19th century, Northern and Southern Methodists followed Asbury’s lead, seeking to prevent a formal schism.

At the same time, Methodism fractured. African Americans in the Methodist Episcopal Church were barred from being ordained as ministers, and church members often worshipped in segregated congregations. This led to the formation of many independent African American Methodist churches – the largest being the African Methodist Episcopal Church, founded by Richard Allen in 1816.

At the 1844 General Conference, the slavery issue boiled over into a major schism. Delegates voted to remove from office a bishop, James Osgood Andrew, because he owned slaves. Andrew’s removal angered Southern delegates who argued that slavery was sanctioned in the Bible. In 1845, Southern Methodist leaders withdrew from the denomination, forming the Methodist Episcopal Church South.

A map of the United States on faded yellow paper with some states outlined in red.
A map from 1901 showing areas of the country with congregations in the Methodist Episcopal Church. Fifteenth Annual Report of the Woman's Home Mission Society of The Methodist Episcopal Church, South/Wikimedia Commons

In 1939, these Northern and Southern churches reunited. Together with another Protestant denomination with historical ties to Methodism, the Evangelical United Brethren, they then combined to form the UMC in 1968.

Debating homosexuality

In 1972, the General Conference adopted a formal statement asserting that homosexuality was “incompatible with Christian teaching.” Subsequent conferences tightened these restrictions, notably in 1984, when the church barred what it called “self-avowed practicing homosexuals” from being ordained.

Since the 1970s, groups on both sides of this issue have mobilized. An organization called the Reconciling Ministries Network has worked to bring together UMC congregations who support the full inclusion of LGBTQ+ people. Conservative groups, meanwhile, such as a caucus called the Good News Movement, have campaigned to enforce the existing LGBTQ+ prohibitions.

In 1996, the General Conference added legislation prohibiting clergy from conducting same-sex weddings – though the number who did so increased significantly.

In recent decades, members of many U.S. churches, including United Methodists, have shown greater acceptance toward LGBTQ+ people. The 2016 election of Karen Oliveto as the first openly gay bishop of any gender in the UMC marked these shifting attitudes.

A man in a suit and glasses speaks into a microphone in front of a crowded room of seated people.
Rev. Jeffrey Kuan wears a prayer stole in support for LGBTQ+ acceptance as he speaks at the UMC General Conference in 2004. AP Photo/Keith Srakocic

Conservatives continue to oppose reforms, including a growing number of United Methodists from outside the U.S – an increasing portion of the church. For example, many African United Methodists come from nations with strict laws banning homosexuality. Of the 862 delegates attending the upcoming General Conference, 380 will be from outside the U.S. Nearly 300 of these delegates will come from Africa.

At an impasse

Conflicts between conservatives and progressives came to a head in 2019, when bishops called a special conference in hopes of preventing a schism.

Their council endorsed what was called the One Church Plan, which would have allowed United Methodists in different countries more autonomy. Specifically, they could determine how to address questions on sexuality.

However, delegates voted overwhelmingly for what was called The Traditional Plan. This kept the church’s restrictions against LGBTQ+ people in place, while calling for more punitive measures against pastors who conducted same-sex weddings.

The 2019 conference then passed a resolution giving local congregations the option to leave the UMC over matters of sexuality. Congregations were given until the end of 2023 to disaffiliate, although the ramifications were to be finalized at the 2020 General Conference.

A man in a suit speaks at a pulpit in front of a room of standing people, most of whom are older.
The Rev. Bill Farmer speaks to Grace Methodist Church in Homosassa Springs, Fla., which is affiliated with the Global Methodist Church. AP Photo/Chris O'Meara, File

This session was repeatedly postponed, however, due to COVID-19. Doubting that U.S.-based leaders would uphold the prohibitions of the Traditional Plan, a group of conservatives formed the Global Methodist Church in March 2022, triggering an exodus of several local churches. As of early 2024, more than 7,600 churches have disaffiliated, representing roughly a fourth of United Methodist congregations.

Uncertain future

Ahead of the 2024 General Conference, conservatives have indicated their intention to lobby to extend the deadline for disaffiliation. Some progressive United Methodists, frustrated by the UMC’s persistent refusal to expand LGBTQ+ rights, have considered forming a third Methodist denomination.

Regardless of what happens in Charlotte, Methodist churches will face challenging futures.

A bird's-eye view of a church sanctuary, with half or more of the pews empty.
Rev. Chris Morgan leads his congregation at Christ United Methodist Church in Bethel Park, Pa., in 2022. AP Photo/Philip G. Pavely

Unlike 1844, when many churches were growing rapidly, the current schism comes as American Protestantism is shrinking. This includes not only mainline Protestant denominations, but more conservative churches as well. In 1968, United Methodist membership in the U.S. was 10.3 million; at the end of 2018, it was 6.7 million.

Another serious challenge is the rising percentage of Americans with no religious affiliation, commonly called religious nones – many of whom are disillusioned by anti-LGBTQ+ policies.

Regardless of the General Conference’s outcome, Methodists face a religious landscape unknown to their 19th century predecessors.

Christopher H. Evans does not work for, consult, own shares in or receive funding from any company or organization that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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