Brainless Embryos Suggest Bioelectricity Guides Growth

The tiny tadpole embryo looked like a bean. One day old, it didn’t even have a heart yet. The researcher in a white coat and gloves who hovered over it made a precise surgical incision where its head would form. Moments later, the brain was gone, but the embryo was still alive.

The brief procedure took Celia Herrera-Rincon, a neuroscience postdoc at the Allen Discovery Center at Tufts University, back to the country house in Spain where she had grown up, in the mountains near Madrid. When she was 11 years old, while walking her dogs in the woods, she found a snake, Vipera latastei. It was beautiful but dead. “I realized I wanted to see what was inside the head,” she recalled. She performed her first “lab test” using kitchen knives and tweezers, and she has been fascinated by the many shapes and evolutionary morphologies of the brain ever since. Her collection now holds about 1,000 brains from all kinds of creatures.

Quanta Magazine


Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

This time, however, she was not interested in the brain itself, but in how an African clawed frog would develop without one. She and her supervisor, Michael Levin, a software engineer turned developmental biologist, are investigating whether the brain and nervous system play a crucial role in laying out the patterns that dictate the shapes and identities of emerging organs, limbs and other structures.

For the past 65 years, the focus of developmental biology has been on DNA as the carrier of biological information. Researchers have typically assumed that genetic expression patterns alone are enough to determine embryonic development.

To Levin, however, that explanation is unsatisfying. “Where does shape come from? What makes an elephant different from a snake?” he asked. DNA can make proteins inside cells, he said, but “there is nothing in the genome that directly specifies anatomy.” To develop properly, he maintains, tissues need spatial cues that must come from other sources in the embryo. At least some of that guidance, he and his team believe, is electrical.

In recent years, by working on tadpoles and other simple creatures, Levin’s laboratory has amassed evidence that the embryo is molded by bioelectrical signals, particularly ones that emanate from the young brain long before it is even a functional organ. Those results, if replicated in other organisms, may change our understanding of the roles of electrical phenomena and the nervous system in development, and perhaps more widely in biology.

“Levin’s findings will shake some rigid orthodoxy in the field,” said Sui Huang, a molecular biologist at the Institute for Systems Biology. If Levin’s work holds up, Huang continued, “I think many developmental biologists will be stunned to see that the construction of the body plan is not due to local regulation of cells … but is centrally orchestrated by the brain.”

Bioelectrical Influences in Development

The Spanish neuroscientist and Nobel laureate Santiago Ramón y Cajal once called the brain and neurons, the electrically active cells that process and transmit nerve signals, the “butterflies of the soul.” The brain is a center for information processing, memory, decision making and behavior, and electricity figures into its performance of all of those activities.

But it’s not just the brain that uses bioelectric signaling—the whole body does. All cell membranes have embedded ion channels, protein pores that act as pathways for charged molecules, or ions. Differences between the number of ions inside and outside a cell result in an electric gradient—the cell’s resting potential. Vary this potential by opening or blocking the ion channels, and you change the signals transmitted to, from and among the cells all around. Neurons do this as well, but even faster: To communicate among themselves, they use molecules called neurotransmitters that are released at synapses in response to voltage spikes, and they send ultra-rapid electrical pulses over long distances along their axons, encoding information in the pulses’ pattern, to control muscle activity.

Levin has thought about hacking networks of neurons since the mid-1980s, when he was a high school student in the suburbs near Boston, writing software for pocket money. One day, while browsing a small bookstore in Vancouver at Expo 86 with his father, he spotted a volume called The Body Electric, by Robert O. Becker and Gary Selden. He learned that scientists had been investigating bioelectricity for centuries, ever since Luigi Galvani discovered in the 1780s that nerves are animated by what he called “animal electricity.”

However, as Levin continued to read up on the subject, he realized that, even though the brain uses electricity for information processing, no one seemed to be seriously investigating the role of bioelectricity in carrying information about a body’s development. Wouldn’t it be cool, he thought, if we could comprehend “how the tissues process information and what tissues were ‘thinking about’ before they evolved nervous systems and brains?”

He started digging deeper and ended up getting a biology doctorate at Harvard University in morphogenesis—the study of the development of shapes in living things. He worked in the tradition of scientists like Emil du Bois-Reymond, a 19th-century German physician who discovered the action potential of nerves. In the 1930s and ’40s, the American biologists Harold Burr and Elmer Lund measured electric properties of various organisms during their embryonic development and studied connections between bioelectricity and the shapes animals take. They were not able to prove a link, but they were moving in the right direction, Levin said.

Before Genes Reigned Supreme

The work of Burr and Lund occurred during a time of widespread interest in embryology. Even the English mathematician Alan Turing, famed for cracking the Enigma code, was fascinated by embryology. In 1952 he published a paper suggesting that body patterns like pigmented spots and zebra stripes arise from the chemical reactions of diffusing substances, which he called morphogens.

“This electrical signal works as an environmental cue for intercellular communication, orchestrating cell behaviors during morphogenesis and regeneration.”

Masayuki Yamashita

But organic explanations like morphogens and bioelectricity didn’t stay in the limelight for long. In 1953, James Watson and Francis Crick published the double helical structure of DNA, and in the decades since “the focus of developmental biology has been on DNA as the carrier of biological information, with cells thought to follow their own internal genetic programs, prompted by cues from their local environment and neighboring cells,” Huang said.

The rationale, according to Richard Nuccitelli, chief science officer at Pulse Biosciences and a former professor of molecular biology at the University of California, Davis, was that “since DNA is what is inherited, information stored in the genes must specify all that is needed to develop.” Tissues are told how to develop at the local level by neighboring tissues, it was thought, and each region patterns itself from information in the genomes of its cells.

The extreme form of this view is “to explain everything by saying ‘it is in the genes,’ or DNA, and this trend has been reinforced by the increasingly powerful and affordable DNA sequencing technologies,” Huang said. “But we need to zoom out: Before molecular biology imposed our myopic tunnel vision, biologists were much more open to organism-level principles.”

The tide now seems to be turning, according to Herrera-Rincon and others. “It’s too simplistic to consider the genome as the only source of biological information,” she said. Researchers continue to study morphogens as a source of developmental information in the nervous system, for example. Last November, Levin and Chris Fields, an independent scientist who works in the area where biology, physics and computing overlap, published a paper arguing that cells’ cytoplasm, cytoskeleton and both internal and external membranes also encode important patterning data—and serve as systems of inheritance alongside DNA.

And, crucially, bioelectricity has made a comeback as well. In the 1980s and ’90s, Nuccitelli, along with the late Lionel Jaffe at the Marine Biological Laboratory, Colin McCaig at the University of Aberdeen, and others, used applied electric fields to show that many cells are sensitive to bioelectric signals and that electricity can induce limb regeneration in nonregenerative species.

According to Masayuki Yamashita of the International University of Health and Welfare in Japan, many researchers forget that every living cell, not just neurons, generates electric potentials across the cell membrane. “This electrical signal works as an environmental cue for intercellular communication, orchestrating cell behaviors during morphogenesis and regeneration,” he said.

However, no one was really sure why or how this bioelectric signaling worked, said Levin, and most still believe that the flow of information is very local. “Applied electricity in earlier experiments directly interacts with something in cells, triggering their responses,” he said. But what it was interacting with and how the responses were triggered were mysteries.

That’s what led Levin and his colleagues to start tinkering with the resting potential of cells. By changing the voltage of cells in flatworms, over the last few years they produced worms with two heads, or with tails in unexpected places. In tadpoles, they reprogrammed the identity of large groups of cells at the level of entire organs, making frogs with extra legs and changing gut tissue into eyes—simply by hacking the local bioelectric activity that provides patterning information.

And because the brain and nervous system are so conspicuously active electrically, the researchers also began to probe their involvement in long-distance patterns of bioelectric information affecting development. In 2015, Levin, his postdoc Vaibhav Pai, and other collaborators showed experimentally that bioelectric signals from the body shape the development and patterning of the brain in its earliest stages. By changing the resting potential in the cells of tadpoles as far from the head as the gut, they appeared to disrupt the body’s “blueprint” for brain development. The resulting tadpoles’ brains were smaller or even nonexistent, and brain tissue grew where it shouldn’t.

Unlike previous experiments with applied electricity that simply provided directional cues to cells, “in our work, we know what we have modified—resting potential—and we know how it triggers responses: by changing how small signaling molecules enter and leave cells,” Levin said. The right electrical potential lets neurotransmitters go in and out of voltage-powered gates (transporters) in the membrane. Once in, they can trigger specific receptors and initiate further cellular activity, allowing researchers to reprogram identity at the level of entire organs.

Lucy Reading-Ikkanda/Quanta Magazine

This work also showed that bioelectricity works over long distances, mediated by the neurotransmitter serotonin, Levin said. (Later experiments implicated the neurotransmitter butyrate as well.) The researchers started by altering the voltage of cells near the brain, but then they went farther and farther out, “because our data from the prior papers showed that tumors could be controlled by electric properties of cells very far away,” he said. “We showed that cells at a distance mattered for brain development too.”

Then Levin and his colleagues decided to flip the experiment. Might the brain hold, if not an entire blueprint, then at least some patterning information for the rest of the body, Levin asked—and if so, might the nervous system disseminate this information bioelectrically during the earliest stages of a body’s development? He invited Herrera-Rincon to get her scalpel ready.

Making Up for a Missing Brain

Herrera-Rincon’s brainless Xenopus laevis tadpoles grew, but within just a few days they all developed highly characteristic defects—and not just near the brain, but as far away as the very end of their tails. Their muscle fibers were also shorter and their nervous systems, especially the peripheral nerves, were growing chaotically. It’s not surprising that nervous system abnormalities that impair movement can affect a developing body. But according to Levin, the changes seen in their experiment showed that the brain helps to shape the body’s development well before the nervous system is even fully developed, and long before any movement starts.

The body of a tadpole normally develops with a predictable structure (A). Removing a tadpole’s brain early in development, however, leads to abnormalities in tissues far from the head (B).

That such defects could be seen so early in the development of the tadpoles was intriguing, said Gil Carvalho, a neuroscientist at the University of Southern California. “An intense dialogue between the nervous system and the body is something we see very prominently post-development, of course,” he said. Yet the new data “show that this cross-talk starts from the very beginning. It’s a window into the inception of the brain-body dialogue, which is so central to most vertebrate life as we know it, and it’s quite beautiful.” The results also raise the possibility that these neurotransmitters may be acting at a distance, he added—by diffusing through the extracellular space, or going from cell to cell in relay fashion, after they have been triggered by a cell’s voltage changes.

Herrera-Rincon and the rest of the team didn’t stop there. They wanted to see whether they could “rescue” the developing body from these defects by using bioelectricity to mimic the effect of a brain. They decided to express a specific ion channel called HCN2, which acts differently in various cells but is sensitive to their resting potential. Levin likens the ion channel’s effect to a sharpening filter in photo-editing software, in that “it can strengthen voltage differences between adjacent tissues that help you maintain correct boundaries. It really strengthens the abilities of the embryos to set up the correct boundaries for where tissues are supposed to go.”

To make embryos express it, the researchers injected messenger RNA for HCN2 into some frog egg cells just a couple of hours after they were fertilized. A day later they removed the embryos’ brains, and over the next few days, the cells of the embryo acquired novel electrical activity from the HCN2 in their membranes.

The scientists found that this procedure rescued the brainless tadpoles from most of the usual defects. Because of the HCN2 it was as if the brain was still present, telling the body how to develop normally. It was amazing, Levin said, “to see how much rescue you can get just from very simple expression of this channel.” It was also, he added, the first clear evidence that the brain controls the development of the embryo via bioelectric cues.

As with Levin’s previous experiments with bioelectricity and regeneration, many biologists and neuroscientists hailed the findings, calling them “refreshing” and “novel.” “One cannot say that this is really a step forward because this work veers off the common path,” Huang said. But a single experiment with tadpoles’ brains is not enough, he added — it’s crucial to repeat the experiment in other organisms, including mammals, for the findings “to be considered an advance in a field and establish generality.” Still, the results open “an entire new domain of investigation and new of way of thinking,” he said.

Experiments on tadpoles reveal the influence of the immature brain on other developing tissues, which appears to be electrical, according to Levin and his colleagues. Photo A shows the appearance of normal muscle in young tadpoles. In tadpoles that lack brains, the muscles fail to develop the correct form (B). But if the cells of brainless tadpoles are made to express ion channels that can restore the right voltage to the cells, the muscles develop more normally ©.
Celia Herrera-Rincon and Michael Levin

Levin’s research demonstrates that the nervous system plays a much more important role in how organisms build themselves than previously thought, said Min Zhao, a biologist at the University of California, Davis, and an expert on the biomedical application and molecular biophysics of electric-field effects in living tissues. Despite earlier experimental and clinical evidence, “this paper is the first one to demonstrate convincingly that this also happens in [the] developing embryo.”

“The results of Mike’s lab abolish the frontier, by demonstrating that electrical signaling from the central nervous system shapes early development,” said Olivier Soriani of the Institut de Biologie de Valrose CNRS. “The bioelectrical activity can now be considered as a new type of input encoding organ patterning, allowing large range control from the central nervous system.”

Carvalho observed that the work has obvious implications for the treatment and prevention of developmental malformations and birth defects—especially since the findings suggest that interfering with the function of a single neurotransmitter may sometimes be enough to prevent developmental issues. “This indicates that a therapeutic approach to these defects may be, at least in some cases, simpler than anticipated,” he said.

Levin speculates that in the future, we may not need to micromanage multitudes of cell-signaling events; instead, we may be able to manipulate how cells communicate with each other electrically and let them fix various problems.

Another recent experiment hinted at just how significant the developing brain’s bioelectric signal might be. Herrera-Rincon soaked frog embryos in common drugs that are normally harmless and then removed their brains. The drugged, brainless embryos developed severe birth defects, such as crooked tails and spinal cords. According to Levin, these results show that the brain protects the developing body against drugs that otherwise might be dangerous teratogens (compounds that cause birth defects). “The paradigm of thinking about teratogens was that each chemical is either a teratogen or is not,” Levin said. “Now we know that this depends on how the brain is working.”

The body of a tadpole normally develops with a predictable structure (A). Removing a tadpole’s brain early in development, however, leads to abnormalities in tissues far from the head (B).

These findings are impressive, but many questions remain, said Adam Cohen, a biophysicist at Harvard who studies bioelectrical signaling in bacteria. “It is still unclear precisely how the brain is affecting developmental patterning under normal conditions, meaning when the brain is intact.” To get those answers, researchers need to design more targeted experiments; for instance, they could silence specific neurons in the brain or block the release of specific neurotransmitters during development.

Although Levin’s work is gaining recognition, the emphasis he puts on electricity in development is far from universally accepted. Epigenetics and bioelectricity are important, but so are other layers of biology, Zhao said. “They work together to produce the biology we see.” More evidence is needed to shift the paradigm, he added. “We saw some amazing and mind-blowing results in this bioelectricity field, but the fundamental mechanisms are yet to be fully understood. I do not think we are there yet.”

But Nuccitelli says that for many biologists, Levin is on to something. For example, he said, Levin’s success in inducing the growth of misplaced eyes in tadpoles simply by altering the ion flux through the local tissues “is an amazing demonstration of the power of biophysics to control pattern formation.” The abundant citations of Levin’s more than 300 papers in the scientific literature—more than 10,000 times in almost 8,000 articles—is also “a great indicator that his work is making a difference.”

The passage of time and the efforts of others carrying on Levin’s work will help his cause, suggested David Stocum, a developmental biologist and dean emeritus at Indiana University-Purdue University Indianapolis. “In my view, his ideas will eventually be shown to be correct and generally accepted as an important part of the framework of developmental biology.”

“We have demonstrated a proof of principle,” Herrera-Rincon said as she finished preparing another petri dish full of beanlike embryos. “Now we are working on understanding the underlying mechanisms, especially the meaning: What is the information content of the brain-specific information, and how much morphogenetic guidance does it provide?” She washed off the scalpel and took off her gloves and lab coat. “I have a million experiments in my mind.”

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

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The Gift That Keeps On Giving: This Girls Dad Is Still Dressed Up As Dumbledore The Week After Her Birthday, And Now His 2 Friends Are, Too

Okay, now this is totally awesome.

When 9-year-old Tracy Durham celebrated her birthday last week, her dad completely surprised her by dressing up as Dumbledore, her favorite character from the Harry Potter series. Lucky for Tracy, it looks like this is one gift that just keeps on giving, because a week after her birthday, her dad still hasn’t taken the costume off, and his two best buddies are dressed up like Dumbledore as well!

Wow! Looks like Tracy is getting the ultimate Harry Potter experience!

At Tracy’s Harry Potter-themed birthday party last week, her dad, Edgar, took the time to get dressed up in an authentic-looking Dumbledore costume, complete with floor-length purple robes and Dumbledore’s signature long, white beard. But where any average dad would let the fun stop when Tracy’s friends left at the end of the day, Edgar went above and beyond by staying in the costume all night long and even wearing it to church the next morning. Now he’s been in the costume for an entire week straight, and a couple of days ago his friends David and Jerry also showed up in full Dumbledore costumes and they’ve been milling around the house lapsing in and out of British accents ever since!

At this rate, Tracy may just have three Dumbledores hanging around her house forever!

Whether Tracy’s dad and his two friends are shooting pool together in the den, talking basketball at the kitchen table, or all shouting “Expecto Patronum!” at Tracy in unison, all three of them are doing it while sporting Dumbledore’s trademark braided white beard and half-moon spectacles. As a Harry Potter fan, Tracy’s got to be absolutely thrilled!

Yep, this is basically the coolest thing a parent and his two friends could do for a kid. Tracy just might be the luckiest girl in the world!

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Hilarie Burton Candidly Opens Up About Miscarriage While Sharing First Photos Of Miracle Baby

Oh, Hilarie Burton.

Our heart aches, beats, and pumps for you right now.

The 35-year-old actress shared a deeply touching

Following the 2010 birth of their first child, Augustus Morgan, the two actors would soon learn that having another baby proved challenging. While their second little one (a baby girl!) was born on February 16, they experienced deep loss prior to the arrival of their “miracle” baby.

In a post that also serves as their daughter’s introduction to the virtual world, Hilarie courageously opened up about the miscarriages they endured:

As some of you know, @jeffreydeanmorgan is off in Europe getting ready to do some big conventions. And he’s self aware enough to know his track record for “spilling the beans” isn’t so great (bless his heart!). So before he starts tripping up in an attempt to maintain our privacy, he asked that I go ahead and post something about our little girl’s birth. But before I do that, there’s something I really want to say to all the women out there who are trying….. It took a long time for Jeffrey and I to have this baby. The first time I got pregnant, it took a year and a half. I surprised him on Christmas with baby Seahawk booties. We cried. We celebrated. We picked out names. And we lost that baby. More losses followed, and as so many couples know, it was heartbreaking. It still is heartbreaking. And every morning of the five years it took us, I’d open my computer at the kitchen table and see the news and I’d grow bitter over the endless parade of celebrities showing off their bumps and babies. I’d weep out of jealousy for how easy it was for them. Didn’t they know something could go wrong? Didn’t they know that there were other women out there struggling? It pained me to see the corporate sponsored baby showers and magazine covers capitalizing on this human miracle that wasn’t happening for us. So when this pregnancy started, we were cautious. I didn’t want to celebrate for fear of jinxing it. I didn’t want a baby shower. I checked her heartbeat every day, up until the day she was born. And now that she is here, I just stare at her in wonder all day. I see her in her daddy’s arms and I don’t take any of it for granted. She screams bloody murder and I smile because she is so wildly alive. So now that folks know she’s here, I don’t want her birth to cause any other woman to weep at her kitchen table. If anything, my wish is that she would restore hope for others. Fertility is a fickle thing. And for the other couples out there who have had dark days, we want to introduce our miracle baby to you and send you our love and support in finding yours. Please meet George Virginia Morgan. She was born February 16th. Her daddy delivered her. We love her very much.A post shared by Hilarie Burton (@hilarieburton) on Mar 6, 2018 at 10:13am PST

We mourn for your loss, Hilarie.

And we celebrate your miracle! Welcome to a world of possibility, George Virginia Morgan! We’re so happy you’re here.

[Image via Adriana M. Barraza/WENN.]

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Drug errors cause appalling harm – Hunt

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Media captionHealth Secretary Jeremy Hunt discusses deaths caused by drug errors

Drug errors in England cause appalling levels of harm and deaths, Health Secretary Jeremy Hunt says, as data suggests mistakes are being made.

GPs, pharmacists, hospitals and care homes may be making 237 million errors a year – the equivalent of one mistake made for every five drugs handed out.

The study said most caused no problems, but in more than a quarter of cases the mistakes could have caused harm.

Drug errors could be a factor in more than 22,000 deaths a year.

The mistakes include:

  • wrong medications being given
  • incorrect doses dispensed
  • delays in medication being administered

The researchers – drawn from Manchester, Sheffield and York universities – acknowledge that there is limited data in this area so the figures are very much best estimates based on previous research, some of it going back years.

But they believe the data is robust enough to warrant action.

Mr Hunt said: “We are seeing four to five deaths every single day because of errors in prescription, or dispensing, or the monitoring of medications.”

He added that the study was not about blaming NHS staff, but about creating a culture where checks were in place to stop errors happening.

A fifth of the mistakes related to hospital care, including errors made by doctors administering anaesthetic before surgery.

The rest were pretty evenly split between drugs given in the community by GPs and pharmacists, and those handed out in care homes.

In total 1.15 billion drug prescriptions are made each year.

‘My 92-year-old mother got another person’s medication’

Image copyright Other
Image caption The drugs for Catherine Young’s mother, Irene, were mixed up with another patient’s medication

One of the people who suffered from a drug error was Catherine Young’s mother, Irene.

She was living in a care home and was aged 92 when she was given a host of wrong drugs for several weeks after her prescription was mixed up with another patient’s.

It meant she stopped getting steroids for polymyalgia rheumatica, which causes pain, stiffness and inflammation in the muscles around the shoulder, neck and hips.

This caused her to go into withdrawal, while she developed irritation around her eyes because she had started being given eye drops she did not need.

Ms Young, from Suffolk, said the mistake had been missed by the GP, pharmacists and care home staff and spotted only when she had questioned the medication after noticing her mother’s condition had been deteriorating.

“It was down to me, a layman with no medical training, to sound the alarm.

“Thankfully we were able to act in time, but others have not been so lucky.”

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Royal College of Nursing chief executive Janet Davies said the study was “deeply concerning”.

She added: “There is real problems in preserving patient safety when you haven’t got enough staff and when we’ve got the financial pressures we have.”

She said human error is “one of the biggest risks” and that overstretched nursing staff and agency workers put “added risk in” the system, but certainly did not make errors inevitable.

We will do more to tackle this – Hunt

Mr Hunt said he was concerned by the findings – although he pointed out that the research showed this was a global problem and not one unique to the NHS.

“It is a far bigger problem than generally recognised, causing appalling levels of harm and death that are totally preventable.”

In a speech to a patient safety conference in London on Friday, Mr Hunt is expected to outline steps the NHS is taking to reduce mistakes.

These include the continued rollout of the much delayed electronic prescribing – only a third of hospitals have an effective system in place.

The Department of Health and Social Care believe the roll out of electronic prescribing systems across more hospitals could reduce errors by 50%.

In his speech, Mr Hunt will also say there needs to be greater openness about mistakes, so the NHS can learn from them.

A change in the law is being introduced that will mean pharmacists will not be prosecuted for owning up to genuine mistakes.

Prof Helen Stokes-Lampard, of the Royal College of GPs, said doctors “work hard to avoid making mistakes” but were only human.

The “intense pressures” on the front line would also be contributing to the problem, she added.

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These Women Could Lose Their Right to Work in the US

From the street, you can hear children at play. Inside the one-story house in Fremont, California, a fish tank gurgles by the front door. A plastic bin filled with Legos sits in the sun room. Renuka Sivarajan, 37, runs a home daycare here. Her path to this point has been like the stock market of late.

When Sivarajan first came to the US from India, in 2003, she worked for a tech company in Phoenix. After she married, she commuted each weekend to the San Francisco area, where her husband worked as an engineer. When she became pregnant with her son in 2007, she moved to California, giving up her job—and work permit. For three consecutive years, she applied for the same work visa that her husband holds, an H-1B. Each year, she was not picked in the random lottery that allocates these visas. She became depressed.

“There would be days when I would be so dull that I wouldn’t even want to play with my child, my own child,” she says. Sivarajan decided to go back to school, completing courses in early childhood education at a local community college. In 2015, after a years-long push from activists, the Obama administration allowed spouses of certain H-1B holders to obtain work permits. Sivarajan opened her daycare. More recently, she thought about expanding outside her home, to a new center. Then, in December, the Trump administration indicated it may eliminate the work permits for spouses.

“There are days when I can’t sleep properly because it bothers me,” Sivarajan says. “It bothers me to think about the future.” Without a job, she worries about holding onto the house, paying bills. She doesn’t know if finances will force the family to move back to India.

“Legally, I’m not allowed to work if I don’t have a work permit, which means all the 16 children whose families who are dependent on me right now, I have to let them all go. They have to find another provider for themselves. My three employees will lose their jobs,” she says. “Thinking about it makes me sad.”

The Trump administration says it plans to soon end the program allowing Sivarajan and more than 100,000 others to work in the US. Called H-4 EAD, or employment authorization document, the permit is available to the spouses of workers on H-1B visas who are in line for permanent US residency. Many tech companies sponsor and apply for H-1B visas, which are given to high-skilled foreign workers, often engineers.

The Obama administration started the program in 2015 partly due to a backlog in the green card process. Because of a per-country cap, people from populous countries such as India and China must wait years before gaining residency. That also meant spouses had been waiting years before they were eligible to work.

When it established the rule, US Citizenship and Immigration Services said the program would benefit the American economy. Last fall, USCIS indicated it was considering revoking the rule as part of President Trump’s “Buy American, Hire American” executive order.

Shah Peerally, an immigration attorney in Newark, California thinks the government will end the program. “I hope I am wrong, but I think it’s on the way,” he said. The government is still facing a 2015 lawsuit from a group alleging the program is illegal and takes jobs from US citizens. (The group is represented by attorneys from two organizations that the Southern Poverty Law Center classifies as hate groups.)

The Trump administration initially suggested it wanted to end the H-4 EAD program by February, but recently delayed that plan, saying it needed to conduct a new economic analysis. It now hopes to issue a proposal in June. Peerally thinks the administration has already made up its mind. He predicts that unless a lawsuit bogs down the process, the program “will be gone, basically in the next one or two years.” USCIS said in a statement that it is undergoing a “thorough review of employment-based visa program” and said it has not made a final decision.

Meanwhile, in Congress, Senator Orrin Hatch, (R-Utah), introduced an immigration bill that would keep the H-4 EAD program in place. Tech companies have stayed largely quiet on the issue, but an industry group wrote to USCIS in support of the program.

In the last few months, holders of the work permit—a vast majority of whom are women, many with advanced degrees—have ramped up a social-media campaign. They’ve gone to congressional town hall meetings and lobbied members of Congress at their offices, encouraging them to pressure USCIS to halt the rule change and to protect the program through legislation such as Hatch’s. At a recent town hall meeting with US Representative Ro Khanna, (D-California), a staffer asked the several hundred in the crowd how many were affected by the H-4 visa issue. At least two-thirds of the auditorium stood up.

“Most of us are spouses who have not been able to work for so long,” Sivarajan says. “And not all of us know how to advocate for ourselves.”

In conversations, several visa holders in Silicon Valley and one in Georgia speak of uncertainty prompted by the potential repeal of the policy, and question the government’s logic. Because of these work permits, people have bought homes, and moved around the country. Children have been brought into the world. From a range of backgrounds and professions, the visa holders talk of the sacrifices they’ve made, their hopes for the future, and the dignity of work, its inseparability from identity.

Tanya Madan, 28, Mountain View, California

Madan is a recruiter for a staffing company in San Jose. Every day, she helps Americans find work as cashiers, baristas, and clerks. We’re not talking high-profile tech jobs. “Most of them are looking for jobs in retail, restaurants, like, you know, for instance, Starbucks, Macy’s, something like that,” she says.

“When I got my worker permit authorization, it’s like, you know, ‘I got my wings back,’” says Tanya Madan.

Carly Cram

Madan came to the US in 2015, then spent a year at home before her work authorization came through. “When I got my worker permit authorization, it’s like, you know, ‘I got my wings back,’” she says. “I will work to give back something to this country because they’ve given me this great opportunity to work,” she decided. So she volunteered for a year at nonprofit news company as a recruiter. Money was secondary. First came identity. But when she and her husband moved in 2017 from New York to California, mammon reared its ugly head. “God, this area is too expensive!” she realized. So she got a job.

Madan looks back, sadly, on the year when the government did not allow her to work. “The whole year I didn’t know what to do,” she says. “Since I was in India I have been working since I was 18. So sitting at home, devoting my life to kitchen? Household chores? That’s not what I ever dreamed of. I’m a free bird.”

“I have a plan, that probably 10 years from now I would have a separate organization where there would be no fees charged when it comes to looking for a job, or looking for a candidate. It would be a free service. For everybody. Irrespective of what country you’re coming from. So I want to do something. I don’t know. It’s just something in my mind. (Laughs.) But I want to do something. Where people have free access to do their job. I mean, of course, there are staffing companies that make money. I don’t want to do that.”

Sampada Khanapurkar, 37, Cumming, Georgia

Khanapurkar came to the US in 2004. She got her second masters degree at Virginia Tech in analytical chemistry; her first, in India, was in organic chemistry. In Boston, she worked on an H-1B visa for almost six years as a scientist at a biotech firm involved in cancer research. After her son was born in 2013, she quit her job, which changed her visa status to an H-4. The couple moved to Georgia for its lower cost of living. Khanapurkar had a hard time finding a position as a scientist on an H-1B there. By 2016, she had had another child because the new H-4 work permit program meant the couple could again have two incomes. She switched careers. Now Khanapurkar works as a project manager for a workflow-solutions company whose clients do a lot of printing, such as the Boston Globe. Another client is the insurance company known as American Family.

“Right now we just feel not accepted here,” says Sampada Khanapurkar.

Jessie Parks

“We are looking at options. Should we move to Canada, or should we move to New Zealand? Or any other country that’s accepting of us? Right now we just feel not accepted here. Like we are not wanted here. And we are, you know, contributing so much to the economy and being legal citizens, legal immigrants. In spite of that, it’s the addition of being looked down upon. It’s not a good feeling, you know? I mean, I’ve been here so long, I just thought, ‘These people are mine.’ And now people aren’t accepting me. It’s not a good feeling. I told my husband yesterday, if this is how we’re feeling and this is how we’re going to be feeling every single day of our lives, living in fear, never know when our visas will be revoked, never know when we’ll be accepted here legally, in spite of being legal, we might as well go to a place where people are accepting of us.”

Teenu Sharma, 31, Milpitas, California

In India, Sharma worked in insurance. She thought when she came to the US in 2014 that she would be able to find an employer willing to sponsor her for an H-1B visa. She soon realized it was next to impossible without being in tech. (Most petitions for these types of visas are for workers in STEM fields.) Sharma sought to study, but didn’t have the money. When the work permits became available in 2015, she had to return to India for four months for a family crisis, and is still waiting to receive her H-4 EAD. Her dream is to open a restaurant.

“I was totally independent when I was in India. Now I am dependent on everything on my husband,” says Teenu Sharma.

Carly Cram

“I was totally independent when I was in India. Now I am dependent on everything on my husband. Let’s say if I want to buy a gift for my husband on his birthday, on Valentine’s Day, I cannot. Because I don’t have my own bank account. I don’t have my own debit card, credit card. I don’t have anything. So for his gift, I have to ask for money. From him. He’s a wonderful guy, that’s not the problem. But it hurts my dignity. It hurts my independence. I have dreams too. I have skills. I want to realize it for my own sake, for my own career, for the economy as well. And we love America as much as we love our home country.”

Immigration and Tech

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Charlize Theron Explains How Her Mom Became Her Weed Dealer

Charlize Theron likes to get high on her own supply ― from her mother. 

The 42-year-old “Gringo” actress revealed during an appearance on “Jimmy Kimmel Live!” Wednesday that her mom, Gerda, recently started buying her weed. It all started because the two have trouble sleeping, Theron said. They wanted to try a strain of weed that would help, rather than their usual sleep medication.

“Last week she showed up at my house, literally drove in in her little tennis outfit, and brought me a little container and just left it on my kitchen table,” Theron said. “And she was like, ’So I got some blueberry covered chocolate ones, but if you want it faster acting you should go for the mints, ’cause those you suck and it just works faster.”

Theron said she was really happy with the results, and said the remedy “totally works, it’s amazing” and that her sleep is now “incredible.” 

And while she’s willing to share sleep advice, she’s not willing to share her dealer mother. 

“You can’t have her, she’s all mine,” the actress said. 

Kevin Mazur via Getty Images
Charlize Theron (right) with her mother, Gerda, at the Oscars in 2013.

Sounds like we’ll be hearing a lot more weed tips and stories throughout Theron’s press trip for her new movie, “Gringo” — which just happens to be about a pharmaceutical team heading to Mexico to mass-produce a marijuana pill. 

During her Wednesday appearance on “Kimmel,” Theron also opened up about why she stopped smoking pot after a “good solid eight years on the marijuana.” 

“I’m always willing to try anything,” the actress said. “And then my chemistry sort of changed one day and I found myself, like, frozen in front of my fridge for eight hours and I couldn’t speak and it wasn’t fun anymore.” 

In a recent interview with E! News, Theron said she’d been a “wake and baker” for most of her life. 

“I didn’t really mess around with anything until I was much older. But I really appreciated marijuana way more than alcohol or anything else,” that is, until she became “boring on it.”

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5 Awesome Movie Sequels (You Had No Clue Existed)

If Batman taught me anything — besides an expert grasp of the Keysi fighting method — it’s that a movie franchise either dies a hero or lives long enough to see itself become the villain. The longer a successful series stretches on, the more likely it’s going to overstay its welcome, and not even hiring Jeremy Irons will save you. But as with all rules, there are exceptions, and they often show up in the last place any decent person would look. Such as …


Final Destination 5 Has A Genuinely Good Plot Twist

Confession time: I didn’t have to go back and watch the Final Destination sequels. I already knew them by heart. I love these movies. They’re like if Freddy Krueger passionately fucked a Rube Goldberg machine.

But before we get to spoilers, did you know that Final Destination was originally going to be an X-Files episode? Writer Jeffrey Reddick’s first draft was a spec script called “Flight 180,” which later evolved into the film directed by James Wong (who happened to be a producer and director for The X-Files). You can still see story elements in the film that would have gone into the episode, including that plane crash clearly serving as a cold open.

The main character in Final Destination has a premonition of the crash and escapes with a group of classmates before takeoff, thereby causing death to personally hunt them down one by one. Since then, every sequel has featured a group of people unwittingly caught in that hilarious ripple of Benny Hill deaths — including but not limited to elevator decapitations, tanning accidents, and FATAL GYMNASTICS.

New Line Cinema“Oooohhh, and the judges only give her a 7.8.”

That above masterpiece is from Final Destination 5, a film that begins with an oddly accurate bridge collapse. It’s after this disaster that death begins punking our heroes. And while Final Destination 5 could simply coast on the series’ grisly reputation, the writers gave themselves the added challenge of hiding a completely unnecessary plot twist.

You see, one of the B-plots of FD5 is that the protagonist wants to travel to Paris to be some kind of fancy French cook. And when the characters eventually break free of death’s pattern (or so they think), they celebrate by taking that trip … on the plane from the very first movie.

New Line Cinema

Yup, for no reason other than fun, Final Destination 5 is a secret prequel to the original film. It’s a twist that relies on hiding from audiences that a film made in 2011 takes place 11 years earlier, before everyone had flat screen TVs and smartphones. That’s kind of a tall order. And so it might not surprise you to know that the writer behind this film went on to do the screenplay for Arrival, a film more temporally confusing than Doc Brown’s family tree. Hey, and speaking of time travel …


Cinderella III Is A Badass Sci-Fi Thriller About Time Travel

It’s fair to say that most adults pay little attention to the direct-to-DVD Disney sequels. For parents, a movie like Cinderella III is a safe child distraction so they can cry in the pantry between meals. But perhaps it’s the assumed disposability of these movies that creates an opportunity to take insane chances, which is why while the second Cinderella sequel has a Rotten Tomatoes score in the teens and Cinderella III: A Twist In Time is surprisingly well-rated.

Rotten Tomatoes

We open a year after the first film, with Cinders happily living life with her prince while her evil step-family are forced to do all the chores. One of the evil sisters (Anastasia) then learns about the Fairy Godmother, and in a fit of jealousy, steals her magic wand. And so, in the great tradition of Biff Tannen, Cinderella’s evil stepmother uses the same magic that screwed her to go back in time and sabotage the climax of the original film. After preventing Cinderella from trying on the glass slipper, she magically changes the size of Anastasia’s foot, using the Prince’s extraordinary face blindness / foot fetish against him. This is enough to throw everyone into an alternate timeline wherein Cinderella doesn’t live happily ever after and her evil stepsister gets hitched instead.

But before the rice is tossed, Mr. Prince gets cold feet, finding himself attracted to Cinderella despite her not fitting into the stupid shoe. What follows is a wonderful story about two people falling for each other in a way that doesn’t involve cursed gourd travel and crystalline footwear. Oh, and the rodent antics are replaced with Assassin Creed-style action jumps.

Walt Disney Pictures

Walt Disney Pictures

Walt Disney PicturesAnother movie this is better-reviewed than.

So yeah, the movie turns Cinderella into Katniss, and the Prince gets a real personality beyond being a pair of fertile balls strapped to a smile. Hell, even the evil stepsister Anastasia gets a character arc — she’s a hopeless romantic who gets dragged into her mother’s machinations because she likes the Prince’s affection, and ultimately learns that love isn’t worth having if it’s forced. (I’m not crying, you’re crying.)


The 14th Land Before Time Is One Big Callback To The Original

Don Bluth’s The Land Before Time taught a generation that dinosaurs were cool and life is a twisted carnival ride of torment and oblivion. Everyone you know will die, and you will be left alone to stare at your own slowly decaying countenance in a pool of your own tears.

Universal PicturesScrew you, Don Bluth.

Anyway, there are 14 Land Before Time sequels, most of which are garbage for the dumbest of children. And while I can’t say that watching Part 14 was an especially edifying, I was shocked by the film’s narrative competence. 2016’s Land Before Time: Journey Of The Brave mirrors the story of the first film. I have no damn clue if this was intentional, but it was enough to keep me riveted for the entire hour and 22 minute runtime. Here’s what happens:

At some point in the last 13 films, it’s revealed that Littlefoot has a father. And in this film, he goes missing. Everyone assumes the worst, and Littlefoot must once again mourn the loss of a parent the only way he knows how: puddle-sulking.

Universal Pictures

But wait! Littlefoot becomes determined to find his father. And what follows is basically a reverse telling of the first Land Before Time film. Our group of heroes leave the Great Valley to venture into the wasteland. In contrast to the first film, Littlefoot goes on tilt, tells his companions to eat a ripe bundle of veiny dicks, and runs off, because the void is inexorable and you might as well greet it with open arms. It’s like poetry, you guys. There’s even a brand-new version of Sharptooth in the mix.

Universal Pictures“It’s Sharp … everything!”

Littlefoot isn’t going to lose another parent, not even when he finally finds Pop trapped in a farting sea of hot dirt.

Universal PicturesAnd millions of children vow to never heartlessly play “The Floor Is Lava” ever again.

This is exact type of circumstance that originally separated Littlefoot from his mother. Littlefoot’s most existential fears are in full gear, and this little giraffe-lizard saves his father from a searing death. They live happily ever after (or at least until the encroaching wasteland overtakes their grazing grounds and they all starve to death).


The Halloween Series Ended Perfectly With H20

So we’re getting another Halloween film that somehow fits into the already baffling franchise. Sure, why not? Like you, I’m excited to see Jamie Lee Curtis return to the series after all these years … the same way I was excited the first time it happened, in 1998’s Halloween: Water.

Dimension Films

I get that there’s no stopping these films any more than you can scream at rain to turn back into clouds, but it always baffled me how anyone could think we needed more films after Halloween H20: 20 Years Later. It only took four years to get 2002’s Halloween Resurrection, in which Busta Rhymes does multiple comedy bits with Michael Myers. Anyway, H20 begins by showing exactly what the first two Halloweens did to Laurie Strode, who has since changed her name and developed a panic-reducing booze lust. Also, Michael Myers shows ups and pounds an ice skate into Joseph Gordon-Levitt’s skull.

Dimension Films

Dimension Films“Where he stuck the other skate was way more painful.”

It’s dark and hilarious, like a puppeteer’s resume. This opening credits, which recap the earlier films, notably linger on the black, lifeless eyes of Michael Myers.

Dimension Films

Dimension Films“Like a studio exec’s eyes …”

Why am I talking about this? Because the movie is setting up its final scene, which is absolutely the best ending Halloween could’ve asked for. If you don’t remember, Jamie Lee Curtis steals an ambulance containing her (presumed) dead brother. When he comes to, she drives off the road and down a hill, flinging both of them out of the vehicle and ultimately pinning Michael against a tree. With nowhere to go, Michael reaches out for his sister. And in a moment of empathy, Laurie reaches back.

Dimension Films

Well, almost.

Dimension Films

Dimension FilmsThe look of “I’m going to betray you” or “I pooped myself.”

Laurie notices her brother’s eyes, and their familiar lack of expression or pain. So instead of helping him, she opts to ax-slap his stupid William Shatner head into next week.

Dimension Films“OK, now I pooped myself.”

The film ends right there and then, presumably triggering sexual climax for millions of fans. And by God, it should have stayed ended (I’m not even gonna explain how Resurrection got around this). Jamie Lee Curtis came back for a goddamn Halloween film in which her character overcomes her fears and slays her brother once and for all, and the studio had the goddamn audacity to continue the series after that? Shame, Dimension Films. Shame.


Universal Soldier: Day Of Reckoning Is A Masterpiece

Let me tell you about the first five minutes of 2012’s Universal Soldier: Day Of Reckoning. We begin with the POV of a man waking up next to his wife in the middle of the night. His daughter is up too. She tells him that there are “monsters” in the house, so he checks every room to assure the little idiot that it was all a bad dream. Then he walks into the kitchen …

Magnet Releasing

What follows is a continuous POV shot of a man being beaten to near death by a group of ski-masked thugs, which culminates in the bad guys dragging his family into the room with him.

Magnet Releasing

And right before we see them murder his daughter and wife, the main thug bends down in front of him and removes his mask.

Magnet Releasing“Sirprize.”

It’s fucking Jean-Claude Van Damme, you guys. JCVD himself just murdered a woman and child. And this roller coaster is still only ticking up the hill.

I don’t know if you recall the first Universal Soldier, but all you need to know is that it was the film Roland Emmerich made right before blasting off with Stargate and Independence Day. Dolph Lundgren was the villain. It’s exactly the kind of movie that would exist in 1992. And no, Jean-Claude was not evil in that film, but the split-kicking hero, which is one of the many reasons this opening sequence is so incredibly jarring. The other reason is that Day Of Reckoning is surprisingly well-made.

In fact, the movie is downright surreal at times, with one review describing it as “a movie Werner Herzog, David Lynch, and Shivers-era David Cronenberg might make if they teamed up to shoot a Bourne knockoff in Louisiana on a shoestring budget.” And that’s one of two reviews that bring up Lynch as a comparison. Why? Because Universal Soldier: Day Of Reckoning is beautiful bananas. I would add that it evokes vibes of Coppola’s Apocalypse Now, with JCVD playing the role of Walter Kurtz.

Seriously, the majority of this film is about one man’s quest to find JCVD, and when he does, it looks like this:

Magnet Releasing

I wish I could tell you why Van Damme is painted like a half-and-half cookie, but at this point in watching, my mind was far too blown by the macabre tubular-ness of this action spectacle to bother with the petty details.

So how did this happen? Well, for starters, Universal Soldier: Day Of Reckoning is directed by John Hyams, whose father directed Timecop and was therefore bestowed with the genetic gift of Van Damme whispering. Also, Dolph Lundgren comes back, and every performance is somehow wonderful. Without spoiling too much, the journey is paved with PTSD dreams about dead children, mind control hallucinations, and a sporting goods store grapple in which two men duel with baseball bats:

All of this is shot amazingly (no shaky cam or Bourne-style over-cutting), and leads to a solid plot twist and bizarre ending. All in a film shot for only eight million dollars. So step it up, David Lynch. There’s no longer an excuse for experimental indie films not to go hog wild with JCVD spin-kicks.

David will gladly talk to you about Universal Soldier: Day Of Reckoning on his Twitter account.

Get to writing your own great-but-unheard-of sequels with CeltX — here’s a handy guide to it for beginners.

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The Rite Press takes low-tech coffee making to high-tech highs

If coffee be the food of innovation, pour on. Give me excess of it that, surfeiting, the appetite may sicken, and so die. And if you wish to pour me coffee, do so from the Rite Press, a clever hack on the traditional French press that adds a few features that even high-end models don’t have.

The press – which costs $35 for a half-liter model and $40 for the liter model – has hit its goal on Kickstarter and I’ve been able to play with it over the past few weeks. The press features two special features. One is a small, readable thermometer on the plunger that ensures your water temperature is well within the proper range for a good brew. Second, the system includes a magnetic timer that looks like something Hal Solo would use to time his Italian roast.

It also has a very clever removable bottom that lets you clean out the grounds with ease. The Kickstarter ends in thirteen days and they are already well over their goal.

Again, this is some low-tech stuff. You could buy a very basic French press for much less. I particularly like the design here and I suspect we should support the creation of new and unique kitchen gear or else be buried in an avalanche of status quo devices. As a fan of coffee and a fan of good design the RitePress is something I’m happy to get behind.

  1. 1 Liter Stainless Steel Black – In Bed 2

  2. IMG_0256

  3. IMG_8169

  4. IMG_5717

  5. 1 Liter Stainless Steel Black _ Silver

  6. IMG_7478

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Anti-depressants work, major study says

Media playback is unsupported on your device
Media captionProf Andrea Cipriani said it was good news for patients and doctors

Scientists say they have settled one of medicine’s biggest debates after a huge study found that anti-depressants work.

The study, which analysed data from 522 trials involving 116,477 people, found 21 common anti-depressants were all more effective at reducing symptoms of acute depression than dummy pills.

But it also showed big differences in how effective each drug is.

The authors of the report, published in the Lancet, said it showed many more people could benefit from the drugs.

There were 64.7 million prescriptions for the drugs in England in 2016 – more than double the 31 million in 2006 – but there has been a debate about how effective they are, with some trials suggesting they are no better than placebos.

The Royal College of Psychiatrists said the study “finally puts to bed the controversy on anti-depressants”.

The so-called meta-analysis, which involved unpublished data in addition to information from the 522 clinical trials involving the short-term treatment of acute depression in adults, found the medications were all more effective than placebos.

However, the study found they ranged from being a third more effective than a placebo to more than twice as effective.

Lead researcher Dr Andrea Cipriani, from the University of Oxford, told the BBC: “This study is the final answer to a long-standing controversy about whether anti-depressants work for depression.

“We found the most commonly prescribed anti-depressants work for moderate to severe depression and I think this is very good news for patients and clinicians.”

Anti-depressant “stigma”

Media playback is unsupported on your device
Media caption“There’s still a stigma”

Christian Talbot, a comedian, said he first started taking anti-depressants three and a half years ago after he found talking therapies had been ineffective for him.

His doctor told him his depression was due to his low levels of serotonin, which is thought to influence mood, emotion and sleep.

Christian said he had been reluctant to take anti-depressants at first because he feared they might make him “numb” or dull his senses.

But he said when he did take them the results were “immediately beneficial”.

“It wasn’t that I felt a huge change come over me but I did feel literally like there was a weight that came off my shoulders. I was less anxious and felt more even.”

He said he felt there was a stigma around taking the drugs.

“I don’t know if people are afraid of them or they’re embarrassed about them, because it’s a medication just like anything else, except it’s for a mental health issue rather than a physical issue.”

Anti-depressants – the most and least effective

Image copyright Getty Images

The most effective:

  • agomelatine
  • amitriptyline
  • escitalopram
  • mirtazapine
  • paroxetine

The least effective:

  • fluoxetine
  • fluvoxamine
  • reboxetine
  • trazodone

‘Compelling evidence’

The study’s authors said the findings could help doctors to pick the right prescription, but it did not mean everyone should be switching medications.

That is because the study looked at the average effect of drugs rather than how they worked for individuals of different ages or gender, the severity of symptoms and other characteristics.

Researchers added that most of the data in the meta-analysis covered eight weeks of treatment, so the findings might not apply to longer-term use.

And they said it did not mean that anti-depressants should always be the first form of treatment.

At least one million more people in the UK would benefit from treatments, including anti-depressants, they said.

“Medication should always be considered alongside other options, such as psychological therapies, where these are available,” Dr Cipriani added.

You might also be interested in:

Prof Carmine Pariante, from the Royal College of Psychiatrists, said: “This meta-analysis finally puts to bed the controversy on anti-depressants, clearly showing that these drugs do work in lifting mood and helping most people with depression.

“Importantly, the paper analyses unpublished data held by pharmaceutical companies, and shows that the funding of studies by these companies does not influence the result, thus confirming that the clinical usefulness of these drugs is not affected by pharma-sponsored spin.”

However, Prof Pariante said the paper did not improve understanding of how to help patients who had treatment-resistant depression and who were not helped by taking any of the 21 tested drugs.

Glyn Lewis, professor of psychiatric epidemiology at University College London, said the “excellent” study provided “compelling evidence” for the effectiveness of anti-depressants.

He added: “Anti-depressants often receive a ‘bad press’ but this paper shows they have a role in the management for people with depression.”

How have you coped with your depression? Please share your experience with us by emailing

Please include a contact number if you are willing to speak to a BBC journalist. You can also contact us in the following ways:

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This video of a corgi riding a one-eyed pony was made for the internet

The internet loves corgis—especially videos of corgis doing silly things. Usually, these videos don’t depict the jolly, short-legged dogs as particularly agile. But maybe we underestimated them.

A video captured by a 22-year-old woman in Missouri shows a corgi riding on the back of a pony. Excuse me, a one-eyed pony named Cricket. Callie Schenker says the corgi belongs to her neighbors, and the dog apparently snuck onto her property and befriended Cricket while all the humans weren’t watching.


News anchor Katy Andersen tweeted a link to the video on Wednesday, and it quickly spread across the internet. Over the last couple of days, the video was retweeted by more than 50,000 people on Twitter. If you watched the video, you probably have a few questions. How the hell did this corgi climb onto the pony’s back? Did the pony bow down? Did the corgi bounce from the fence to the pony’s back? Can the pony and the corgi communicate with each other?

It’s probably best not to think too much about the logistics of this video. Just enjoy it as a break from the daily soul-crushing news cycle. The internet is certainly enjoying it:









One person made a request: Set the video to Ginuwine’s 1996 hit song “Pony.”



Ask, and the internet delivers. Here’s the video with “Pony” playing in the background.


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