James' World 2

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Two conversations, two different outcomes. The first was talking with a plumber about how to run waste lines for a bathroom addition. I thought we should use an existing vent pipe for a washer box that would be abandoned. He thought we should run two new vent pipes.

“I think one of those is overkill,” I said. “I don’t see why it’s necessary.”

He stood up, crossed his arms, and stared at me.

“You saying I don’t know my job?” he said.

The second was talking to a cabinet supplier about trim. She was adamant I only needed crown molding.

“Huh,” I said. “It’s interesting you say that. I was sure you would say I needed starter crown, too.”

She explained why I didn’t. Ceiling height. A wider built-in lip at the top of the cabinet for nailing. A more streamlined profile. I didn’t necessarily agree, but when I said, “I feel sure I’ll end up being wrong… but I think I would like you to include it, just in case,” she laughed and said, “Absolutely. And even though we don’t normally do this, you can return it when you realize I’m right.”

In the first example, I turned a disagreement into an argument by challenging—or at least appearing to challenge—the person’s knowledge and experience. While I didn’t mean to, for him, my choice of words made it personal, and he responded emotionally.

The second is an example of what Amanda Ripley, the author of High Conflict: Why We Get Trapped and How We Get Out, calls productive conflict. I could have just said, “Tell me why you feel that way,” but that could have come across as challenging (in both scenarios).

Instead, I reframed disagreement as curiosity. Softening it with words like, “It’s interesting you say that,” and delivering those words with a genuine sense of curiosity, showed I was interested. I was open. I didn’t want to argue. I wanted to learn. She also responded emotionally, but this time in a good way—because I had implicitly shown I respected her (possibly greater) knowledge.

Science backs up that approach. A study published in Cognitive Science found that rather than trying to win an argument, “arguing” to learn makes other people more receptive to your views. As the researchers write:

Participants who engaged in cooperative interactions were less inclined to agree that there was an objective truth about that topic than were those who engaged in a competitive interaction…. When people are in cooperative arguments, they see the truth as more subjective.

In sum, people change their evaluation of truth to be consistent with the goals of their particular argumentative mindset.

Or in non-researcher-speak, challenge me and I’m unlikely to change my mind, even in the face of better evidence. Make me feel you want to learn, though, and I’ll be more open to learning as well. (To quote the eminent philosopher Rocky Balboa, “If I can change, youse can change.”)

Of course, “It’s interesting you say that…” aren’t the only words you can use to avoid making people feel defensive. Here are some other sentence starters Ripley recommends. (Again, you can’t just parrot the words to seem curious—you also have to be curious.)

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In the age of precision medicine, targeted drugs are transforming cancer treatment. But cancer cells persist in many patients, even in breast cancer, where much-lauded hormone therapies and targeted therapies have had a huge impact. Despite these and other advances in precision medicine, the five-year survival rate for advanced breast cancer is still only about 30 percent. 

To help more patients whose breast cancer recurs, scientists have developed targeted therapies, which typically rely on monoclonal antibodies or small-molecule inhibitors to stop runaway cell growth. A new type of therapy takes a different approach. Unlike prior generations of small-molecule drugs, a new class of compounds called protein degraders not only bind to cancer-driving target proteins—they spur cells to digest them.

This two-pronged attack hits an essential signaling pathway that drives many breast cancers that are more resistant to standard treatments. The goal for this tactic is to be as specific as possible, in order to leave more healthy cells unharmed. This advance is unleashing opportunities for therapeutic approaches that might “prolong life with fewer treatment side effects,” says Katherine Ansley, a clinical associate professor of hematology and oncology at Wake Forest University School of Medicine.

An elusive target

Discovered in the mid-1980s, PI3K is an intracellular enzyme, part of an essential pathway that signals healthy cells to grow and proliferate. Several isoforms of PI3K exist, each with distinct and essential roles. Mutations in one of them, known as PI3K-alpha, result in overactive growth signaling in as many as 40 percent of women with the most common form of breast cancer—tumors that grow in response to the hormones estrogen or progesterone, and produce low levels of human epidermal growth factor receptor 2 (HER2). 

Although drugs exist that can block mutant PI3K, breast cancer can outsmart such therapies. What’s more, earlier drugs that attack this pathway shut down multiple isoforms of PI3K, inadvertently disabling pathways that healthy cells rely on. This low level of selectivity has made prior generations of PI3K inhibitors overly toxic. It also made scientists think that the PI3K signaling pathway would be difficult to target.

Researchers pressed on anyway, and developed various inhibitors that selectively target specific PI3K isoforms, and since 2014 the U.S. Food and Drug Administration has approved nearly half a dozen isoform-selective PI3K inhibitors. 

To unlock the full therapeutic potential of targeting PI3K and to reach more patients, the key is “treating the right population with ever more selective compounds,” says Jennifer Schutzman, lead medical director at Genentech. “More selective inhibitors may be safer.”

A two-part mechanism

Genentech started working on PI3K nearly two decades ago, focusing mainly on an isoform that is often dysregulated in a common form of breast cancer, called hormone-receptor-positive (HR-positive), HER2-negative breast cancer. Genentech scientists sought to target the PI3K pathway with exquisite precision. To do so, they tweaked chemical structures in a painstaking search for molecules that bind primarily to the PI3K-alpha isoform, while leaving other PI3K isoforms largely untouched. Over about 20 years, the Genentech team gradually developed molecules that bind to the PI3K-alpha isoform with high selectivity.

But the research also led to a big scientific surprise. The researchers discovered that the small molecules do more than bind to the protein—they also induce the cell to digest it.

That discovery marked a turning point, says Marie-Gabrielle Braun, a chemist and senior principal scientist at Genentech who designed the compounds. “It showed that we had done something fundamentally different than what had been achieved with prior generations of these compounds, and it gave us strong confidence that we could potentially have better outcomes in the clinic.” 

The dual-action mechanism of this new class of compounds, now known as “protein degraders,” offered unanticipated therapeutic opportunities. It meant that treatments “might be even safer and more efficacious,” Schutzman says. “That’s because you’re taking what you know is a growth-promoting signal and essentially getting rid of it for a more durable period of time. So, you may get increased benefits for patients.”

Expanding use

In addition to treatments for later stages of cancer, Ansley is hopeful that some forms of PI3K protein degraders might offer new treatment options at earlier stages of the disease. In such cases, the aim of treatment is to stop or slow tumor-cell proliferation so that oncologists can regain control of the disease. 

To bring these new treatments to the clinic, oncologists can screen for eligible patients by testing for gene mutations that generate the abnormal protein by having biopsy samples tested using next-generation sequencing. They can also collect cell-free DNA (cfDNA) from a blood sample and have it analyzed using one of several commercially available kits that use the polymerase chain reaction (PCR), which is less invasive and less expensive, but also less comprehensive, than sequencing.  

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The Taurid meteor shower will be visible in the night sky for the next week for the phenomenon’s annual appearance.

Earth passes through the debris left behind by comets every fall from September to November and the meteor shower was expected to be most visible beginning early Tuesday through Nov. 12.

The phenomenon gets its name from the path it travels across the sky from the constellation Taurus, the Bull. Watchers can see more meteors, or fireballs, the higher the shower’s radiants are in the sky.

Bill Cooke, the head of NASA’s Meteoroid Environment Office, told ABC News that the Taurid meteor is the result of the Comet Encke, one of the largest in the solar system. Encke is a small portion of an even larger comet that broke up about 10,000 years ago.

“What makes them so special is the Taurids are big,” Cooke said. “They’re big pieces of debris, and they produce these very spectacular fireballs. You don’t want to look at Taurus, because the meteor coming from there will have short trains and be faint.”

The Taurid meteor shower comes in two waves, the Southern Taurids and the Northern Taurids.

Visibility for the Southern Taurids was expected to be best Monday and Tuesday, as a dimmer moon — just 11% full — won’t obstruct visibility.

The Northern Taurids are expected to reach their peak next on Nov. 11-12 but the moon will be 79% full during that period which will harm visibility.

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From three meteor showers to a planetary alignment right next to a famous constellation, here are the top astronomy events to mark on your November 2024 calendar.

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The neuron, the specialized cell type that makes up much of our brains, is at the center of today’s neuroscience. Neuroscientists explain perception, memory, cognition, and even consciousness itself as products of billions of these tiny neurons busily firing their tiny “spikes” of voltage inside our brain.

These energetic spikes not only convey things like pain and other sensory information to our conscious mind, but they are also in theory able to explain every detail of our complex consciousness.

At least in principle. The details of this “neural code” have yet to be worked out.

While neuroscientists have long focused on spikes travelling throughout brain cells, “ephaptic” field effects may really be the primary mechanism for consciousness and cognition. These effects, resulting from the electric fields produced by neurons rather than their synaptic firings, may play a leading role in our mind’s workings.

In 1943 American scientists first described what is known today as the neural code, or spike code. They fleshed out a detailed map of how logical operations can be completed with the “all or none” nature of neural firing—similar to how today’s computers work. Since then neuroscientists around the world have engaged in a vast endeavor to crack the neural code in order to understand the specifics of cognition and consciousness.

To little avail. “The most obvious chasm in our understanding is in all the things we did not meet on our journey from your eye to your hand,” confessed neuroscientist Mark Humphries in 2020’s The Spike, a deep dive into this journey: “All the things of the mind I’ve not been able to tell you about, because we know so little of what spikes do to make them.”

Brain researchers have long acknowledged that there are a number of ways other than firing by which neurons could communicate, including the little-known mechanism known as ephaptic coupling. This coupling results from electromagnetic (EM) fields at the medium and large scales of the brain interacting, alongside much smaller scale fields accompanying synaptic spikes (which themselves result from a type of highly localized EM field activity) operating at nanometer scales.

Retinal neurons, for example, operate without any neural firing. These cells employ a type of electrodiffusion, the diffusion of charged particles without synapses, the connection points between neurons. Electrodiffusion passes along a signal to the optic nerve at very fast rates and with high bandwidth. We couldn’t see without this.

The “ephaptic” in ephaptic coupling simply means “touching.” Though not well-known, ephaptic field effects result from the textbook electric and magnetic interactions that power our cells. Intriguing experimental results suggest these same forces play a bigger role in the brain than one suspected and perhaps even in consciousness.

Ephaptic field effects first came to my attention in a significant way with a remarkable 2019 paper from the Case Western Reserve laboratory of Dominique Durand. That lab demonstrated that the mouse cortex was affected without synaptic connections—by definition, ephaptic field interactions. This remarkable effect was found by the Durand team after they cut a slice of mouse hippocampus in half and then measured the voltage potential going up and down the slice. There wasalmost no change in that measured voltage even after the slice was fully severed, demonstrating a strong influence from ephaptic fields.

The influence did, they found, wane after a certain distance, as we’d expect. Once the cut slices were separated by 400 microns or more, the ephaptic field effect mostly disappeared.

These results were considered so remarkable by peer reviewers that they required the Durand lab to replicate the results not once but twice before they approved publication of the paper. One scholar stated at the time of the paper’s publication that the findings of Chiang and colleagues “should probably (and quite literally) electrify the field.”

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Disrupting the Workplace

I’ve been a manager of a small group in a large organization for several years. In general, my direct reports have been easy to manage; they are conscientious, competent, seasoned professionals. Among them, but not as easily managed, is a longtime employee with chronic health conditions that have gotten worse and impacted her dependability. She has personal circumstances that have added to her unreliability.

We’re an office responsible for producing analytic reports large and small. Some have hard deadlines. I prefer to assign people projects they can invest in and own. Unfortunately, we often need to change focus to respond to changing deadlines and priorities from higher-ups. I try to assign my challenging team member projects with long lead times. Even so, her unreliability means that I have needed to reassign her projects frequently in order to meet deadlines. I spend a lot more time managing work assignments as a result (or just doing the project myself). Sometimes, after I’ve reassigned one of her projects because she says she is not able to work, she shows up. I can either return a project to her, taking it back from another staff member whom I’ve had to redirect from one of their projects, or give her a new, lower-priority project.

I’m trying to figure out whether I should be changing my approach to managing people or to managing the work. Any perspective you can offer would be most welcome. I value this employee and her contributions, but she is taxing me.

— Anonymous

You ask some interesting questions — and some really complicated ones. There’s so much going on here, and I’m not sure I can address all your points in a helpful way. But here goes.

One missing piece of information is whether or not you’ve already had a conversation with this employee. Is she aware of the impact she’s been having? Even if it has come up before, I think you need to have a conversation with her about your concerns. But I would urge you to make that conversation about what you describe as her “inconsistency” — not her illness. It doesn’t sound like she’s making mistakes so much as being unable to make time for the job; in other words, when she’s actually doing her job, she’s doing it well. And you value her for it.

But before initiating that conversation, I think you need to acknowledge the somewhat loaded terms you are using to describe this worker, among them “challenging” and “unreliable.” As you point out, this employee has health problems that affect her ability to work. But the way you describe her makes it sound almost like you resent her — or perhaps don’t fully believe her. (Your reference to her showing up to work after she says she is unable to do so suggests you may not trust her.) So your own feelings toward her may be something you need to explore on your own.

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Photo illustration by Margeaux Walter for The New York Times

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The rock, with its striking black-and-white pattern, resembles alpine granite and has caught the attention of NASA’s Jet Propulsion Laboratory. After being spotted by Perseverance’s Mastcam-Z camera, the team decided to investigate it more closely. The unusual appearance of the rock contrasts sharply with the typical Martian terrain, making it a particularly compelling subject for study. The discovery was made in the Jezero Crater, an area where Perseverance has been searching for ancient sedimentary rocks.

Perseverance’s Next Steps on Mars

Perseverance, which landed in the Jezero Crater in 2021, has already collected samples of ancient river sediments. Now, the rover is climbing to higher elevations in search of new geological clues. Earlier in June 2024, while exploring Mount Washburn, the rover discovered another white rock composed of feldspar and pyroxene, similar to Freya Castle but smaller. Spectrographic analysis of this new find could provide more insights into its mineral composition and how it fits into Mars’ geological history.

Theories on Freya Castle’s Formation

Freya Castle is believed to be a metamorphic rock, formed through intense heat and pressure, which could offer valuable information about Mars’ volcanic past. Given that the Jezero Crater primarily contains sedimentary layers, it’s likely that the rock fell into the crater from higher elevations. Scientists suggest that the rock could have been displaced during a meteor impact or volcanic event millions of years ago, making it a potential key to understanding Mars’ dynamic geological processes.

Unlocking Mars’ Geological Secrets

Scientists are eager to discover more rocks like Freya Castle to help unravel the geological history of Mars. A larger collection of similar rocks might reveal whether they were unearthed by an impact event or transported during a significant volcanic eruption. In either case, this find represents an exciting opportunity to learn more about the Red Planet’s past and its ongoing geological evolution.

Freya Castle could provide important clues about Mars’ complex history. As Perseverance continues its mission, it will be fascinating to see what other discoveries lie ahead.

How do you think these new findings will shape our understanding of Mars?

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Fly above Zhangjiajie’s stunning sandstone peaks, famously inspiring the floating Hallelujah Mountains in “Avatar.” This breathtaking drone footage reveals the ethereal beauty and majestic pillars of China’s enchanting landscape. Experience the mystical allure of Zhangjiajie from a bird’s-eye view with this captivating aerial footage.

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Avatar’s Inspiration: China’s Zhangjiajie Sandstone Peaks

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Parenting a flock of Northern Bald Ibises is a demanding job. For the past six months, biologists Barbara Steininger and Helena Wehner have spent every day hand-feeding and raising dozens of these endangered chicks. They couldn’t pass their fostering duties off on anyone else during that time—the juvenile birds needed to imprint on them and them alone.

Steininger and Wehner then took to the skies to guide their young charges on the birds’ first migration. In mid-August, they climbed onboard a microlight aircraft in Rosegg, Austria, to start their approximately 2,800-kilometer journey, which ended on October 3 at a wintering site in Andalusia, Spain. There the two foster parents said their final goodbye to the birds that they helped raise.

“At the end, you have to release them in the wintering site and accept that they are now independent and don’t need you anymore,” says Johannes Fritz, who leads the team reintroducing Northern Bald Ibises to the wild in Europe and has been piloting the microlight aircraft on these guided migrations since 2004.

Bald Ibis Migration

Each fall, when the days grow shorter and the weather cooler, the ibises’ migratory instinct kicks in, priming them to seek out a warmer climate to spend the winter. Normally parents would guide their young on their first migration to show them the route. But the birds’ knowledge of their flight path has been largely lost. That’s because the species has been hunted nearly to extinction in its native habitat of North Africa, Central Europe, and the Middle East. In Europe, the species was in trouble as early as 1504, when the Archbishop of Salzburg decreed it illegal to shoot the birds. Despite this ban and other early conservation efforts, the Northern Bald Ibis was last seen in the wild in Europe in 1621, and only a small number have survived, mainly in Morocco.

Today, thanks to careful management and reintroduction efforts, some small sedentary (nonmigrating) populations live in the wild in Türkiye and Spain. But their inability to migrate might actually threaten their survival. Migratory birds evolved to reproduce in one climate and spend the winter in another. Splitting their time between two habitats can give them better access to food and higher reproductive success, explains Ana González-Prieto, an avian ecologist at the Canadian Wildlife Service, who is not involved in the reintroduction effort.

To have the best shot at success in the wild, Northern Bald Ibis populations need to migrate, Fritz says. So his team has taken on the responsibility of teaching young birds the route themselves. They were initially inspired by the 1996 movie Fly Away Home, in which a girl and her father help a flock of geese migrate using an ultralight aircraft. The movie was based on the work of the late Bill Lishman, a sculptor and filmmaker who used such an aircraft to teach captive-raised birds to migrate. Lishman co-founded Operation Migration, an organization that deployed bird-costumed scientists to guide endangered birds such as Whooping Cranes, once nearly extinct, on migratory routes across North America.

Fly Away Home with Bald Ibises

This method, called human-led migration, is both resource- and time-intensive, but for the Bald Ibises, it appears to be working. The process starts in the spring with foster parents who hand-rear chicks taken from captive-bred populations. Then, come late summer, the conservation team sets out on its route. A microlight aircraft powered by a propellor and kept aloft by a large yellow parachute takes off, soaring hundreds of meters above the ground. It flies at the speed of the birds, no faster than 50 kilometers per hour. The flying contraption seats two people—Fritz, who got his pilot’s license for this very purpose, and one of the two foster parents, who trade off on sky duty.

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The ideal family road trip begins with two simple things: an open road and a full backseat. The direction the trip takes, however, is almost entirely up to planning. And sure, maybe you’ve thought of the essentials—the snacks, the toys, the fully-charged tablets—but there’s bound to be something you’ve missed.

That’s why we put together a complete checklist of everything to consider before leaving for your family vacation, including expert advice on packing smart, staying safe, keeping kids entertained, and setting road trip rules for a smooth journey.

1. Focus on Car Safety

Begin with a thorough inspection of your road trip car. Check the tires, mirrors, fluids, and lights to ensure everything is functioning properly. Tire pressure and tread depth affect your control over the car, your lights help other drivers see you, and properly adjusted mirrors make certain that you see them. Additionally, maintaining your fluid levels—like coolant, engine oil, and brake fluid— keeps your engine running smoothly throughout your trip.

For more information on car safety checks, view this guide by the Department of Motor Vehicles.

2. Stock Up on Supplies

Pack enough supplies to last the length of your trip, and research stores along the route in case you need to pick something up. When traveling with young kids, keep the most important supplies within arm’s reach.

“I make sure they have everything they need right next to them so they don’t need to get out of their seats,” says mother of two and long-time traveler Emma Scott-Child, who runs a website for parents about crafting, design, and kid-wrangling called Ladyland. “Each kid has a backpack with all their things in them, including a water bottle.”

Must-have supplies might include:

• A bathroom bag with essentials like diapers, wipes, sanitary pads, a portable potty, wet wipes, or a fold-out changing table
• A clean-up kit with your favorite cleaning supplies, including a non-toxic all-purpose spray, microfiber towels, and bleach wipes
• Lots of water to keep kids properly hydrated, which helps regulate their body temperature and aids in digestion1
• A car window shade to block the sun from beaming through the backseat windows (it also protects your little ones from any unnecessary sunburns)
• A small trash bag for waste
• Chargers with car adaptors
• Blankets, pillows, and warm coats
• Hand sanitizer
• Car sickness medicine if your family gets queasy
• Car seat organizers
• A sick bag if your child is prone to nausea, suggests Scott-Child

3. Get Enough Sleep and Stretch When Possible

Getting enough sleep is important for a successful drive, as it helps you stay alert and reduces the risk of an accident. The National Heart, Lung, and Blood Institute recommends that adults aim for 7 to 9 hours of sleep per night.2 “Sleep deprivation is associated with an increased risk of car accidents,” says Dr. Luster.

Moreover, stretching is crucial. Aim to stretch before the trip and during any breaks, as long drives can cause tension from sitting in place for extended periods. This can lead to muscle stiffness, reduced blood circulation, and unnecessary pressure on your joints.

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