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Blood tests are currently one-size-fits-all − machine learning can pinpoint what’s truly ‘normal’ for each patient

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theconversation.com – Brody H. Foy, Assistant Professor of Laboratory Medicine and Pathology, University of Washington – 2024-12-11 10:03:00

Blood tests are essential tools in medicine.
Bloomberg Creative/Bloomberg Creative Photos via Getty Images

Brody H. Foy, University of Washington

If you’ve ever had a doctor order a blood test for you, chances are that they ran a complete blood count, or CBC. One of the most common blood tests in the world, CBC tests are run billions of times each year to diagnose conditions and monitor patients’ health.

But despite the test’s ubiquity, the way clinicians interpret and use it in the clinic is often less precise than ideal. Currently, blood test readings are based on one-size-fits-all reference intervals that don’t account for individual differences.

I am a mathematician at the University of Washington School of Medicine, and my team studies ways to use computational tools to improve clinical blood testing. To develop better ways to capture individual patient definitions of “normal” lab values, my colleagues and I in the Higgins Lab at Harvard Medical School examined 20 years of blood count tests from tens of thousands of patients from both the East and West coasts.

In our newly published research, we used machine learning to identify healthy blood count ranges for individual patients and predict their risk of future disease.

Clinical tests and complete blood counts

Many people commonly think of clinical tests as purely diagnostic. For example, a COVID-19 or a pregnancy test comes back as either positive or negative, telling you whether you have a particular condition. However, most tests don’t work this way. Instead, they measure a biological trait that your body continuously regulates up and down to stay within certain bounds.

Your complete blood count is also a continuum. The CBC test creates a detailed profile of your blood cells – such as how many red blood cells, platelets and white blood cells are in your blood. These markers are used every day in nearly all areas of medicine.

Blood tube on top of print out of lab results
You probably had a CBC test run for your annual physical.
peepo/E+ via Getty Images

For example, hemoglobin is an iron-containing protein that allows your red blood cells to carry oxygen. If your hemoglobin levels are low, it might mean you are iron deficient.

Platelets are cells that help form blood clots and stop bleeding. If your platelet count is low, it may mean you have some internal bleeding and your body is using platelets to help form blood clots to plug the wound.

White blood cells are part of your immune system. If your white cell count is high, it might mean you have an infection and your body is producing more of these cells to fight it off.

Normal ranges and reference intervals

But this all raises the question: What actually counts as too high or too low on a blood test?

Traditionally, clinicians determine what are called reference intervals by measuring a blood test in a range of healthy people. They usually take the middle 95% of these healthy values and call that “normal,” with anything above or below being too low or high. These normal ranges are used nearly everywhere in medicine.

But reference intervals face a big challenge: What’s normal for you may not be normal for someone else.

Nearly all blood count markers are heritable, meaning your genetics and environment determine much of what the healthy value for each marker would be for you.

At the population level, for example, a normal platelet count is approximately between 150 and 400 billion cells per liter of blood. But your body may want to maintain a platelet count of 200 – a value called your set point. This means your normal range might only be 150 to 250.

Differences between a patient’s true normal range and the population-based reference interval can create problems for doctors. They may be less likely to diagnose a disease if your set point is far from a cutoff. Conversely, they may run unnecessary tests if your set point is too close to a cutoff.

Lab tests are interpreted based on reference intervals.

Defining what’s normal for you

Luckily, many patients get blood counts each year as part of routine checkups. Using machine learning models, my team and I were able to estimate blood count set points for over 50,000 patients based on their history of visits to the clinic. This allowed us to study how the body regulates these set points and to test whether we can build better ways of personalizing lab test readings.

Over multiple decades, we found that individual normal ranges were about three times smaller than at the population level. For example, while the “normal” range for the white blood cell count is around 4.0 to 11.0 billion cells per liter of blood, we found that most people’s individual ranges were much narrower, more like 4.5 to 7, or 7.5 to 10. When we used these set points to interpret new test results, they helped improve diagnosis of diseases such as iron deficiency, chronic kidney disease and hypothyroidism. We could note when someone’s result was outside their smaller personal range, potentially indicating an issue, even if the result was within the normal range for the population overall.

The set points themselves were strong indicators for future risk of developing a disease. For example, patients with high white blood cell set points were more likely to develop Type 2 diabetes in the future. They were also nearly twice as likely to die of any cause compared with similar patients with low white cell counts. Other blood count markers were also strong predictors of future disease and mortality risk.

In the future, doctors could potentially use set points to improve disease screening and how they interpret new test results. This is an exciting avenue for personalized medicine: to use your own medical history to define what exactly healthy means for you.The Conversation

Brody H. Foy, Assistant Professor of Laboratory Medicine and Pathology, University of Washington

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Infectious diseases killed Victorian children at alarming rates — their novels highlight the fragility of public health today

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theconversation.com – Andrea Kaston Tange, Professor of English, Macalester College – 2024-12-11 07:40:00

Thomas Worth’s 1872 illustration for the Household Edition of The Old Curiosity Shop highlights her grandfather’s grief at losing Little Nell.
Thomas Worth via George P. Landow/Victorian Web

Andrea Kaston Tange, Macalester College

Modern medicine has enabled citizens of wealthy, industrialized nations to forget that children once routinely died in shocking numbers. Teaching 19th-century English literature, I regularly encounter gutting depictions of losing a child, and I am reminded that not knowing the emotional cost of widespread child mortality is a luxury.

In the first half of the 19th century, between 40% and 50% of children in the U.S. didn’t live past the age of 5. While overall child mortality was somewhat lower in the U.K., the rate remained near 50% through the early 20th century for children living in the poorest slums.

Threats from disease were extensive. Tuberculosis killed an estimated 1 in 7 people in the U.S. and Europe, and it was the leading cause of death in the U.S. in the early decades of the 19th century. Smallpox killed 80% of the children it infected. The high fatality rate of diphtheria and the apparent randomness of its onset caused panic in the press when the disease emerged in the U.K. in the late 1850s.

Multiple technologies now prevent epidemic spread of these and other once-common childhood illnesses, including polio, tetanus, whooping cough, measles, scarlet fever and cholera.

Closed sewers protect drinking water from fecal contamination. Pasteurization kills tuberculosis, diphtheria, typhoid and other disease-causing organisms in milk. Federal regulations stopped purveyors from adulterating foods with the chalk, lead, alum, plaster and even arsenic once used to improve the color, texture or density of inferior products. Vaccines created herd immunity to slow disease spread, and antibiotics offer cures to many bacterial illnesses.

As a result of these sanitary, regulatory and medical advances, child mortality rates have sat below 1% in the U.S. and U.K. since the 1930s.

Victorian novels chronicle the terrible grief of losing children. Depicting the cruelty of diseases largely unfamiliar today, they also warn against being lulled into thinking that child deaths can never be inevitable again.

Routine death meant relentless grief

Novels tapped into communal fears as they mourned fictional children.

Little Nell, the angelic figure at the center of Charles Dickens’ wildly popular “The Old Curiosity Shop,” fades away from an unnamed illness over the last few installments of this serialized novel. When the ship carrying the printed pages with the final part of the story pulled into New York, people apparently shouted from the docks, asking if she had survived. The public investment in, and grief over, her death reflects a shared experience of helplessness: No amount of love can save a child’s life.

Eleven-year-old Anne Shirley of “Green Gables” fame became a hero for pulling 3-year-old Minnie May through a dramatic battle with diphtheria. Readers knew this as a horrendous illness in which a membrane blocks the throat so effectively that a child will gasp to death.

Children were familiar with disease risks. While typhus runs rampant in “Jane Eyre,” killing nearly half the girls at their charity school, 13-year-old Helen Burns is struggling against tuberculosis. Ten-year-old Jane is filled with horror at the possible loss of the only person who has ever truly cared for her.

A young girl, perhaps eight years old, dressed in a dark dress, holds a younger girl, possibly three years old and dressed in white, on her lap
A.D. Webster, ‘young girl and her deceased sister; Anderson siblings,’ carte-de-visite, Constantine, Michigan: ca. 1860s-1870.
Mark A. Anderson Collection of Post-Mortem Photography/William L. Clements Library, University of Michigan

An entire chapter deals frankly and emotionally with all this dying. Jane cannot bear separation from quarantined Helen and seeks her out one night, filled with “the dread of seeing a corpse.” In the chill of a Victorian bedroom, she slips under Helen’s blankets and tries to stifle her own sobs as Helen is overtaken with coughing. A teacher discovers them the next morning: “my face against Helen Burns’s shoulder, my arms round her neck. I was asleep, and Helen was – dead.”

The disconcerting image of a child nestled in sleep against another child’s corpse may seem unrealistic. But it is very like the mid-19th-century memento photographs taken of deceased children surrounded by their living siblings. The specter of death, such scenes remind us, lay at the center of Victorian childhood.

Fiction was not worse than fact

Victorian periodicals and personal writings remind us that death being common did not make it less tragic.

Darwin agonized at losing “the joy of the Household,” when his 10-year-old daughter Annie succumbed to tuberculosis in 1851.

The weekly magazine “Household Words” reported the 1853 death of a 3-year-old from typhoid fever in a London slum contaminated by an open cesspool. But better housing was no guarantee against waterborne infection. President Abraham Lincoln was “convulsed” and “unnerved,” his wife “inconsolable,” watching their son Willie, 11, die of typhoid in the White House.

Excerpt from a yellowed page of text
This ‘Household Words’ report on the coroner’s inquest into the child’s death from typhoid fever gives a grim picture of the lack of sanitation in the neighborhood.
Household Words, January 1853, p.10, CC BY-SA

In 1856, Archibald Tait, then headmaster of Rugby and later Archbishop of Canterbury, lost five of his seven children in just over a month to scarlet fever. At the time, according to historians of medicine, this was the most common pediatric infectious disease in the U.S. and Europe, killing 10,000 children per year in England and Wales alone.

Scarlet fever is now generally curable with a 10-day course of antibiotics. However, researchers warn that recent outbreaks demonstrate we cannot relax our vigilance against contagion.

Forgetting at our peril

Victorian fictions linger on child deathbeds. Modern readers, unused to earnest evocations of communal grief, may mock such sentimental scenes because it is easier to laugh at perceived exaggeration than to frankly confront the specter of a dying child.

“She was dead. Dear, gentle, patient, noble Nell was dead,” Dickens wrote in 1841, at a time when a quarter of all the children he knew might die before adulthood. For a reader whose own child could easily trade places with Little Nell, becoming “mute and motionless forever,” the sentence is an outpouring of parental anguish.

These Victorian stories commemorate a profound, culturally shared grief. To dismiss them as old-fashioned is to assume they are outdated because of the passage of time. But the collective pain of a high child mortality rate was eradicated not by time, but by effort. Rigorous sanitation reform, food and water safety standards, and widespread use of disease-fighting tools like vaccines, quarantine, hygiene and antibiotics are choices.

And the successes born of these choices can unravel if people begin choosing differently about health precautions.

While tipping points differ by illness, epidemiologists agree that even small drops in vaccine rates can compromise herd immunity. Infectious disease experts and public health officials are already warning of the dangerous uptick of diseases whose horrors 20th century advances helped wealthy societies forget.

People who want to dismantle a century of resolute public health measures, like vaccination, invite those horrors to return.The Conversation

Andrea Kaston Tange, Professor of English, Macalester College

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Pearl Young, the first woman to work in a technical role at NASA, overcame barriers and ‘raised hell’ − her legacy continues today

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theconversation.com – Caitlin Milera, Research Assistant Professor of Aerospace, University of North Dakota – 2024-12-10 07:44:00

Caitlin Milera, University of North Dakota

Thirteen years before any other woman joined the National Advisory Committee for Aeronautics – or the NACA, NASA’s predecessor – in a technical role, a young lab assistant named Pearl Young was making waves in the agency. Her legacy as an outspoken and persistent advocate for herself and her team would pave the way for women in science, technology, engineering and mathematics for decades to come.

My interest in Young’s story is grounded in my own identity as a woman in a STEM field. I find strength in sharing the stories of women who made lasting impacts in STEM. I am the director of the NASA-fundedNorth Dakota Space Grant Consortium, where we aim to foster an open and welcoming environment in STEM. Young’s story is one of persistence through setbacks, advocacy for herself and others, and building a community of support.

Facing challenges from the beginning

Young was a scientist, an educator, a technical editor and a researcher. Born in 1895, she was no stranger to the barriers that women faced at the time.

In the early 20th century, college degrees in STEM fields were considered “less suited for women,” and graduates with these degrees were considered unconventional women. Professors who agreed to mentor women in advanced STEM fields in the 1940s and 1950s were often accused of communism.

In 1956, the National Science Foundation even published an article with the title: “Women are NOT for Engineering.”

Despite society’s sexist standards, Young earned a bachelor’s degree in 1919 with a triple major in physics, mathematics and chemistry, with honors, from the University of North Dakota. She then began her decades-long career in STEM.

A group of people standing outside a plane holding a sign that says 'Aloha from Hilo'
An avid traveler, Pearl Young – waving at the top of the stairs – traveled to Hawaii on a UND alumni trip in 1960.
Pearl Young Papers collection in UND’s Special Collections

Becoming a technical editor

Despite the hostile culture for women, Young successfully navigated multiple technical roles at the NACA. With her varied expertise, she worked in several divisions – physics, instrumentation and aerodynamics – and soon noticed a trend across the agency. Many of the reports her colleagues wrote weren’t well written enough to be useful.

In a 1959 interview, Young spoke of her start at the NACA: “Those were fruitful years. I was interested in good writing and suggested the need for a technical editor. The engineers lacked the time to make readable reports.”

Three years after voicing her suggestion, Young was reassigned to the newly created role of assistant technical editor in the publications section in 1935. After six years in that role, Young earned the title of associate technical editor in 1941.

In 1941, the NACA established the Aircraft Engine Research Laboratory, now known as NASA Glenn Research Center, in Cleveland. This new field center needed experienced employees, so two years later, NACA leadership invited Young to lead a new technical editing section there.

A black and white photo of ten women, with five standing behind five seated at a table.
Pearl Young, seated in the front row, far right, with the technical editing section at the Aircraft Engine Research Laboratory. The AERL’s Wing Tips described Young’s office as one which embodied ‘constant vigilance’ and encompassed a ‘rigidly trained crew.’
NASA Glenn Research Center Archives

It was at the Aircraft Engine Research Laboratory that Young published her most notable technical work, the Style Manual for Engineering Authors, in 1943. NASA’s History Office even referred to Young as the architect of the NACA technical reports system.

Young’s style manual allowed the agency to communicate technological progress around the globe. This manual included specific formatting rules for technical writing, which would increase consistency for engineers and researchers reporting their data and experimental results. It was essential for efficient World War II operations and was translated into multiple languages.

But it wasn’t until after this publication that Young finally received the promotion to full technical editor, 11 years after she voiced the need for the role at the agency. She was the first person to hold this role, but she had to start at the assistant level, then move up to associate before receiving the full technical editor designation.

Pearl Young ‘raising hell’

Perhaps the most noteworthy piece of Young’s story is her character. While advocating for herself and her colleagues, Young often had to challenge authority.

She stood up for her editing section when male supervisors wrongfully accused them of making mistakes. She wrote official proposals to properly classify her office in the research division at the Aircraft Engine Research Laboratory. She regularly acknowledged the contributions of her entire team for the achievements they shared.

She also secured extra personnel to lessen unbearable workloads and wrote official memorandums to ensure that her colleagues earned rightful promotions. Young often referred to these actions as “raising hell.”

A letter typed on a typewriter, which includes the sentence 'one false move on their part and I'll raise hell.'
Excerpt of Pearl Young’s letter to colleague and friend Viola Ohler Phillips, stating she’ll ‘raise hell’ if the Washington office refused to follow proper technical editing practices.
NASA Glenn Research Center Archives

The archival documents I’ve analyzed indicate that Young’s performance at the NACA was exemplary throughout her career. In 1967, she was awarded the University of North Dakota’s prestigious Sioux Award in recognition of her professional achievements and service to the university.

In 1995, and again in 2014, NASA Langley Research Center dedicated a theater in her name. The new theater is located in NASA’s Integrated Engineering Services Building.

In 2015, Young was inducted into the inaugural NASA/NACA Langley Hall of Honor. But throughout her career, not all of her colleagues shared this complimentary view of Young and her work.

One of Young’s supervisors in 1930 thought it necessary to assess her “attitude” and fitness as an employee in her progress report – and justified his position by typing these additional words into the document himself.

Later that year, Young requested time off – likely for the holiday season – prompting a different supervisor to draft an official memorandum to the engineer in charge, a position akin to today’s NASA center director. He referred to Young’s “attitude” in requesting to use her vacation days.

A scanned file reads 'this employee's attitude is to take legally all that is possible.'
A 1930 memorandum to the engineer in charge, from the official personnel folder of Pearl Irma Young, describes her ‘attitude.’
National Archives and Records Administration – National Personnel Records Center

Women not welcome in STEM

While sexism in STEM has shifted its forms over time, gender-based inequities still exist. Women in STEM frequently confront microaggressions, marginalization and hostile work environments, including unequal pay, lack of recognition and additional service expectations.

Women often lack supportive social networks and encounter other systemic barriers to career advancement, such as not being recognized as an authority figure, or the double standard of being perceived as too aggressive instead of as a leader.

Women of color, women who belong to LGBTQ+ communities and women who have one or more disabilities face even more barriers rooted in these intersectional identities.

One of the ways to combat these inequities is to call attention to systemic barriers by sharing stories of women who persisted in STEM – women like Pearl Young.The Conversation

Caitlin Milera, Research Assistant Professor of Aerospace, University of North Dakota

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Hypnosis is not just a parlor trick or TV act − science shows it helps with anxiety, depression, pain, PTSD and sleep disorders

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theconversation.com – David Acunzo, Assistant Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia – 2024-12-10 07:43:00

Although hypnosis can help with a number of medical conditions, it doesn’t work for everything.
Paula Connelly/iStock via Getty Images Plus

David Acunzo, University of Virginia

We’ve all seen it, typically on television or on stage: A hypnotist selects a few members from the audience, and with what seems to be little more than a steely stare or a few choice words, they’re suddenly “under the spell.” Depending on what the hypnotist suggests, the participants laugh, dance and perform without inhibition.

Or perhaps you’ve experienced hypnosis another way – with a trip to a hypnotherapist for a series of sessions to help you stop smoking, lose weight, manage pain or deal with depression. This is no longer unusual; thousands of Americans have done the same thing. And many were helped.

Hypnosis has been found to be effective for treating irritable bowel syndrome, and it may be beneficial for weight reduction, sleep disorders and anxiety. For mild to moderate depression in adults, hypnotherapy is as effective as cognitive behavioral therapy, and it can help with depression in children. Hypnosis is also used to treat phobias, PTSD and to control pain during surgery and dental procedures in both adults and children.

Yet despite the evidence, its widespread use and its growing popularity, hypnosis is still viewed with skepticism by some scientists, and with curiosity by much of the public. As a researcher studying altered states from a cognitive and neuroscientific perspective, I’m happy to help pull back the curtain to show you how hypnosis works.

In a comfortable office setting, a woman lies down on a couch, with a therapist sitting nearby in a chair.
People are more hypnotizable if they are receptive to the therapy.
PeopleImages/iStock via Getty Images Plus

A hypnotherapy session

In simple terms, hypnosis is a procedure that helps people imagine different experiences that feel very real. When that occurs, the person can be said to be in a state of hypnosis.

Little is known about what characterizes a hypnotic state in terms of brain activity, but neuroimaging studies indicate a decrease in activity in the parts of the brain responsible for self-referential thought and daydreaming, and increased links between the parts responsible for attention and action.

These results are consistent with the idea that people who are hypnotized are in a state that inhibits internal thoughts and other distractions, such as bodily sensations or noises, that may interfere with the hypnosis.

A therapist’s first set of suggestions typically includes the “hypnotic induction,” which helps the subject increase their responsiveness to other suggestions. An induction may be like this: “I will now count from 5 to 1. At every count, you will feel even more relaxed, and that you are going deeper and deeper into hypnosis.”

When responding to suggestions, the subject’s experience feels involuntary. That is, it’s happening to them, rather than generated by them. This is known as the classical suggestion effect. Following a suggestion to move their arm, the subject may feel as though their arm rises on its own, rather than being raised of their own volition.

For perceptual suggestions, the experience can feel quite real and distinct from voluntary imagination. If I ask you to imagine hearing a dog barking outside, it requires an effort, and the experience does not feel like there’s really a dog barking outside. But through hypnotic suggestion, responsive subjects will feel like they hear a dog barking, and they won’t be cognizant of any effort to make it happen.

What makes people hypnotizable?

You can’t force anyone to be hypnotized. Willingness to participate, a positive attitude, motivation and expectation are hugely important. So is the ability to set aside the fact that the situation is imaginative. It’s like when you become fully absorbed with the story and characters in a movie – so absorbed you forget you’re in a theater.

Good rapport with the therapist is also critical. If you refuse to cooperate or decide hypnosis won’t work, it won’t. A good comparison may be meditation: You can listen to a meditation recording, but if you’re unwilling to follow the instructions, or if you’re unmotivated or distracted, it won’t have any effect.

Few traits predict whether someone is easily hypnotizable, but people are not equal in their ability to respond to hypnotic suggestions. Some people vividly experience a wide array of suggestions; others, not nearly as much. There are indications that women respond slightly better to hypnotic suggestions than men, and that peak hypnotizability occurs during late childhood and early teenage years.

From a neuroscientific perspective, it appears that hypnotic suggestions do not act directly on our executive functions, but rather on our self-monitoring functions. That is, hypnosis does not directly decide our behaviors for us. Rather, it modifies how the brain monitors what it’s doing. So when the hypnotist suggests that you raise your arm, you’re still the one making that decision – although your experience may seem like the arm is moving by itself.

Some myths and realities about a hypnotherapy session.

Exposure therapy, self-hypnosis

The aim of hypnotherapy is to induce changes in negative emotions, perceptions and actions. Suppose you are afraid of public speaking. Through suggestions, the therapist may make you go through the experience of talking in front of an audience. Again, it feels real – your stress level will rise, but ultimately you’ll habituate yourself and learn to cope with the stress, even as the therapist suggests increasingly challenging scenarios.

Hypnosis can also be used as a preparation or replacement for exposure therapy, which is a method to treat phobias or anxiety related to specific situations by progressively exposing the patient to increasingly challenging situations. If you’re afraid of birds, the therapist may suggest you imagine holding a feather; then imagine getting near a bird in a cage; then imagine going to the park and feeding pigeons. This is more effective, and feels more real, than mere visualization.

The hypnotherapist can also teach self-hypnosis techniques. Subjects can learn to induce a state of relaxation that’s associated with a gesture, such as closing the left hand.

Hypnotic suggestions like this decrease anxiety by promoting activation of the parasympathetic nervous system, which stimulates bodily functions during times of rest, such as digestion and sexual arousal, and deactivates the sympathetic nervous system, which stimulates the fight-or-flight response.

Progress can occur after less than 10 sessions with some disorders, such as insomnia in children. But it may take longer for others, such as depression. And just as hypnosis is not suitable for everyone, it’s also not suitable for everything.

What’s more, not all hypnotherapy products on the market are backed by scientific evidence. It is safer to go to a hypnotherapist who’s licensed in your state. You should ask whether they are affiliated with or certified by a professional association of hypnotherapists. You can then confirm their affiliation on the association’s website. For instance, the American Society of Clinical Hypnosis allows you to search members by name.

Although Medicare does not cover hypnotherapy, some private insurance partially covers the costs for some conditions, provided the treatment is performed by a licensed clinical mental health professional. One session will typically cost between US$100 and $250.The Conversation

David Acunzo, Assistant Professor of Psychiatry and Neurobehavioral Sciences, University of Virginia

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