James' World 2

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When it came time for Itzy Morales Pantoja to start her Ph.D. in cellular and molecular medicine, she chose a laboratory that used stem cells—not only animals—for its research. Morales Pantoja had just spent two years studying multiple sclerosis in mouse models. As an undergraduate, she’d been responsible for ­giving the animals painful injections to induce the disease and then observing as they lost their ability to move. She did her best to treat the mice gently, but she knew they were ­suffering. “As soon as I got close to them, they’d start peeing—a sign of stress,” she says. “They knew what was coming.”

Even though the mouse work was emotionally “very, very difficult,” Morales Pantoja remained committed to her research out of a desire to help her sister, who has multiple sclerosis. Three years after the project wrapped up, however, Morales Pantoja was crushed to find that none of her results would be of any direct help to people like her sister. An antioxidant she’d tested seemed promising in mice, but in human samples it was ineffective.

This was a disappointment but not a surprise. Around 90 percent of novel drugs that work in animal models fail in human clinical trials—an attrition rate that contributes to a $2.3-billion average price tag for every new drug that comes to market.

Today Morales Pantoja is a postdoctoral fellow at the Johns Hopkins Center for Alternatives to Animal Testing, where she is helping to develop lab-grown models of the human brain. The goal is to advance scientific understanding of neurodegeneration while moving the field beyond what some researchers see as an antiquated reliance on animal models.

Millions of rodents, dogs, monkeys, rabbits, birds, cats, fish, and other animals are used every year for research purposes worldwide. Exact numbers are hard to come by, but advocacy group Cruelty Free International estimated that 192 million animals were used in 2015. Most of this work occurs in four broad domains: cosmetics and personal products, chemical toxicity testing, drug development, and drug-discovery research.

Animal-based studies have contributed to important findings and lifesaving medical advancements. The COVID vaccines, for instance, were developed in animals, including mice and nonhuman primates. Animal models have also been critical in advancing AIDS drugs and in developing treatments for leukemia and other cancers, among many other uses.

But animal studies often fall short of producing useful results. They may weed out possibly effective drugs or miss toxicity in humans. They have failed to deliver breakthroughs in certain fields of medicine, including neurological conditions. A 2014 study estimated that candidate therapies for Alzheimer’s disease developed in animal models have failed in clinical trials about 99.6 percent of the time. “As questions about human biology and variability get more complex, we are bumping up against the limits of animal models,” says Paul Locke, an environmental health scientist and attorney at the Johns Hopkins Bloomberg School of Public Health. “The thing you run into with animals—and there’s no way to get around this—is that animal biology is just too different from human biology.” Other species are no longer providing the insights about human biology—including at the cellular and subcellular levels—that scientists today need to achieve innovation.

A growing, multidisciplinary community of researchers around the world is investigating alternatives to animal models. Some are motivated by concerns about animal welfare, but for many, sparing the lives of millions of creatures is just an added bonus. They are driven primarily to create technologies and methods that will approximate human biology and variability better than animals do.

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If you’re looking to land a six-figure job or are asking yourself what jobs are in demand, look no further. FlexJobs analyzed its job database from February 1, 2024, through July 30, 2024, to find the most in-demand, fully remote jobs that offer high salaries. The list below features jobs that offer $100,000-plus annual salaries, according to Payscale.

Fully Remote Jobs With $100K+ Salaries

Are you looking to make a high salary, but not sure where to start? These in-demand jobs are a great launching point for your job search.

1. Senior Customer Success Manager

Median salary: $101,184

Senior customer success managers oversee the relationships between a brand and its clients, ensuring satisfaction, retention, and growth. These professionals work closely with sales and support teams to provide strategic solutions, address client needs, and help clients meet their goals with the company’s products or services.

2. Account Director

Median salary: $104,053

Account directors develop and execute strategies to meet clients’ business objectives, ensuring client satisfaction while driving revenue growth. This role often involves coordinating internal teams to manage key client accounts and deliver high-quality services.

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Source Photos: Artem Podrez/Pexels and Mackenzie Marco/Unsplash]

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When doctors ask Sara Gehrig to describe her pain, she often says it is indescribable. Stabbing, burning, aching—those words frequently fail to depict sensations that have persisted for so long they are now a part of her, like her bones and skin. “My pain is like an extra limb that comes along with me every day.”

Gehrig, a former yoga instructor and personal trainer who lives in Wisconsin, is 44 years old. At the age of 17, she discovered she had spinal stenosis, a narrowing of the spinal cord that puts pressure on the nerves there. She experienced bursts of excruciating pain in her back and buttocks and running down her legs. That pain has spread over the years, despite attempts to fend it off with physical therapy, anti-inflammatory injections, and multiple surgeries. Over-the-counter medications such as ibuprofen (Advil) provide little relief. And she is allergic to the most potent painkillers—prescription opioids—which can induce violent vomiting.

Today her agony typically hovers at a 7 out of 10 on the standard numerical scale used to rate pain, where 0 is no pain and 10 is the most severe imaginable. Occasionally her pain flares to a 9 or 10. At one point, before her doctor convinced her to take antidepressants, Gehrig struggled with thoughts of suicide. “For many with chronic pain, it’s always in their back pocket,” she says. “It’s not that we want to die. We want the pain to go away.”

Gehrig says she would be willing to try another type of painkiller, but only if she knew it was safe. She keeps up with the latest research, so she was interested to hear earlier this year that Vertex Pharmaceuticals was testing a new drug that works differently than opioids and other pain medications.

That drug, a pill called VX-548, blocks pain signals before they can reach the brain. It gums up sodium channels in peripheral nerve cells, and obstructed channels make it hard for those cells to transmit pain sensations. Because the drug acts only on the peripheral nerves, it does not carry the potential for addiction associated with opioids—oxycodone (OxyContin) and similar drugs exert their effects on the brain and spinal cord and thus can trigger the brain’s reward centers and an addiction cycle.

In January Vertex announced promising results of clinical trials of VX-548, which it is calling suzetrigine, showing that it dampened acute pain levels by about one half on that 0-to-10 scale. The company is applying for U.S. Food and Drug Administration approval for the drug this year.

Other pain drugs that target sodium channels are now being developed, some by firms motivated by Vertex’s success. Navega Therapeutics, led by biomedical engineer Ana Moreno, is even using molecular-editing tools such as CRISPR to suppress genes involved in chronic pain. “We are definitely hopeful that we can replace opioids, and that’s the goal here,” she says.

One in five U.S. adults—51.6 million people as of 2021—is living with chronic pain. New cases arise more often than other common conditions, such as diabetes, depression, and high blood pressure. Yet pain treatments have not kept pace with the need. There are over-the-counter pills such as aspirin, acet­aminophen (Tylenol), and nonsteroidal anti-inflammatories (NSAIDs) such as Advil. And there are opioids. The glaring inadequacy of existing medications to alleviate human suffering has fueled the ongoing opioid epidemic, which has led to more than 730,000 overdose deaths since its start.

.Samantha Mash

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Your fellow teachers have apparently not gotten the memo yet that it’s 2024 and constantly asking questions about whether someone else is or wants to be pregnant is totally intrusive! But let’s deal with your reality: You may have opened the door for their comments by mentioning you are trying to get pregnant. Still, that doesn’t give them the right to follow up constantly. So many people struggle with infertility—even Democratic vice presidential nominee Tim Walz and his wife have talked openly about their difficulties!—it’s really time to get with the program. You don’t want to be rude, but I think you just have to say, maybe when you are in the teachers’ lounge with a group or at lunch: “I know I mentioned that we were trying for a baby, but we’re taking a break, so it would be great if you didn’t bring it up, as it’s sensitive right now.” That’s not rude. It’s taking care of yourself and your mental health.

That said, I am also concerned about how you’re casting blame for your infertility. Why was it important for Prudie to know that the issue is on your husband’s side? You say it’s “not your body that’s the problem.” Ouch. Imagine if the primary struggle with getting pregnant was on you, and that’s how your husband described it. It takes two (or at least a sperm and an egg) to get pregnant; your infertility is a shared struggle. I suggest you start thinking that way instead of blaming your partner for something outside of his control.

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Most of the matter in our universe is invisible. We can measure the gravitational pull of this “dark matter” on the orbits of stars and galaxies. We can see the way it bends light around itself and can detect its effect on the light left over from the primordial plasma of the hot big bang. We have measured these signals with exquisite precision. We have every reason to believe dark matter is everywhere. Yet we still don’t know what it is.

We have been trying to detect dark matter in experiments for decades now, to no avail. Maybe our first detection is just around the corner. But the long wait has prompted some dark matter hunters to wonder whether we’re looking in the wrong place or in the wrong way. Many experimental efforts have focused on a relatively small number of possible identities for dark matter—those that seem likely to simultaneously solve other problems in physics. Still, there’s no guarantee that these other puzzles and the dark matter quandary are related. Increasingly, physicists ac­­knowl­edge that we may have to search for a wider range of possible explanations. The scope of the problem is both intimidating and exhilarating.

At the same time, we are starting to grapple with the sobering idea that we may never nail down the nature of dark matter at all. In the early days of dark matter hunting, this notion seemed absurd. We had lots of good theories and plenty of experimental options for testing them. But the easy roads have mostly been traveled, and dark matter has proved more mysterious than we ever imagined. It’s entirely possible that dark matter behaves in a way that current experiments aren’t well-suited to detect—or even that it ignores regular matter completely. If it doesn’t interact with standard atoms through any mechanism be­­sides gravity, it will be almost impossible to detect it in a laboratory. In that case, we can still hope to learn about dark matter by mapping its presence throughout the universe. But there is a chance that dark matter will prove so elusive we may never understand its true nature.

On a warm summer evening in August 2022, we huddled with a few other physicists around a table at the University of Washington. We were there to discuss the culmination of the “Snowmass Process,” a year-­long study that the U.S. particle physics community undertakes every decade or so to agree on priorities for future research. We were tasked with summing up the progress and potential of dark ­matter searches. The job of communicating just how many possibilities there are for explaining dark matter, and the many ideas that exist to explore them, felt daunting.

We are at a special moment in the quest for dark matter. Since the 1990s thousands of investigators have searched exhaustively for particles that might constitute dark matter. By now they’ve eliminated many of the simplest, easiest possibilities. Nevertheless, most physicists are convinced dark matter is out there and represents some distinct form of matter.

A universe without dark matter would require striking modifications to the laws of gravity as we ­currently understand them, which are based on Einstein’s general theory of relativity. Updating the ­theory in a way that avoids the need for dark matter—either by adjusting the equations of general relativity while keeping the same underlying framework or by introducing some new paradigm that replaces general relativity altogether—seems exceptionally difficult.

The changes would have to mimic the effects of dark matter in astrophysical systems ranging from giant clusters of galaxies to the Milky Way’s smallest satellite galaxies. In other words, they would need to apply across an enormous range of scales in distance and time, without contradicting the host of other precise measurements we’ve gathered about how gravity works. The modifications would also need to explain why, if dark matter is just a modification to gravity—which is universally associated with all matter—not all galaxies and clusters appear to contain dark matter. Moreover, the most sophisticated attempts to formulate self-consistent theories of modified gravity to explain away dark matter end up invoking a type of dark matter anyway, to match the ripples we observe in the cosmic microwave background, leftover light from the big bang.

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Olena Shmahalo

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Aren’t we stuck with the traits we’re born with?

Actually no, says science. Of course, genetics plays some role in personality. As anyone who has dealt with two or more toddlers can tell you, some of us are born shyer or chattier than others, and these tendencies follow us to some extent throughout our lives.

But when one 64-year-long study examined personality tests for the same individuals over decades, it found basically no relationship between people’s results in their teens and their later years. You are a totally different person at 72 than you were at 14. 

Which invites the question, if personality shifts over time, can you consciously control the process? Can you speed it up? Can you direct it? The answer according to both fascinating personal experience and research appears to be yes.

From teenage slacker to successful achiever 

We’ll start with a personal story from Shannon Sauer-Zavala, a University of Kentucky psychology professor. In a recent Psychology Today post, she explained she definitely wasn’t voted most likely to succeed in high school. In fact she was a shy, messy wallflower who skipped so many math classes she needed to repeat algebra and was repeatedly told by teachers she “wasn’t living up to her potential.”

Now she has a PhD, a TEDx Talk, and a successful career under her belt, and she regularly puts herself out there as living proof that personality change is possible. 

“I love telling people about my own personality change story as a way to bust the myth that traits are set in stone,” she writes. So how did she do it?

Sauer-Zavala seems to have been lucky enough not to be carrying any extreme trauma or a difficult diagnosis. She was just a run-of-the mill, low-motivation high school kid, which allowed her to mold her personality with little more than curiosity, passion, and a series of small, doable behavior shifts. 

First, she stumbled on psychology in college and discovered something she truly was interested in. 

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