Fall is a bad time to hold elections. Here's why.
Millions of Americans didn't vote during the midterms — excuses there are many. Some are valid.
- Usually, only about 40 percent of eligible voters participate in midterm elections.
- Political philosopher John Stuart Mill believed it would be for the collective good if everybody voted.
- Because of logistics, we may need to change the time of year we vote.
There's something strange afoot. It's not how many people love or hate the Brioni suit-wearing man in the Oval Office. It's not even that it's already November — sayonara 2018! It's that, despite the heavy saturation of political news nowadays, millions of Americans ditched the voting booths during this year's midterm elections.
Indeed, as a recent Big Think piece pointed out, "If everybody voted, we would likely see different policies than we see today" — and probably for the better, according to the legendary philosopher John Stuart Mill. So then, why didn't many people across the country show up politically?
Well, first off, there's no blanket answer to cover this elusive group. In the 2016 book Why Don't Americans Vote?: Causes and Consequences, the authors Bridgett King and Kathleen Hale point out, for instance, that as many as 14 percent of studied nonvoters said they didn't cast their ballots because they were sick. As it turns out, voting season parallels flu season. As the Centers for Disease Control and Prevention states on its website, "Influenza activity often begins to increase in October and November."
Photo credit Rawpixel on Unsplash
Though illness, in general, results in many people not participating, it is one of a few given reasons for not voting — or to some, "excuses." For thousands of others Americans, nearly 20 percent of nonvoters, elections come during at a time in their lives when they "don't have time" to engage in the democratic process. As the year winds to an end, and festive holidays rear their expensive albeit rosy-cheeked heads, many working-class Americans focus more on getting work done.
"Having the time to vote, given work schedules [and such], is certainly likely to account for a large amount," says Tess Wise, a Ph.D. candidate in government at Harvard University, regarding the population of nonvoters. Election Day itself is always on a workday, Tuesday.
Wise also tells Big Think that, according to engagement studies, such as those shared in Why Don't Americans Vote, that many nonvoters — as many as 16 percent — felt like their vote didn't matter. In an era where online trolls spew confusion and bots disseminate subterfuge, elections may be a disheartening time.
According to The New York Times, Russian operatives influenced more than 125 million Americans in the 2016 presidential election through targeted fake ads. This said, for nonvoters, one of their big concerns might be whether their filled-out ballots would counter the amount of votes cast by individuals with gimcrack information. This feeling of abulia amid the auburn leaves of November — Seasonal Affective Disorder begins to spike during the fall — leads us our last significant reason many people don't participate.
The blues may beckon as the days get shorter in the fall. Photo credit: Christopher Furlong / Getty Images
About 13 percent of surveyed nonvoters said they didn't participate because they didn't care for the candidates or issues being discussed. This is particularly true for many young voters, who feel politicians don't serve their interests. When you pair an already diminished esteem on the weight of your personal vote with a hopelessness and general uninterest in D.C. theatre — perhaps because of oversaturation of certain news coverage, in some cases — you may get a perfect storm of dissonance to render a legion of potential voters lame.
"In general only about 60 percent of Americans vote in presidential elections and about 40 percent in the midterms," says Wise. "Forty-nine percent in the last election was a record high." Even with what some political experts called "remarkable" grassroots efforts to mobilize voters during the midterms, particularly those in Florida — a proposition passed to restore voting rights to ex-felons — most voting-eligible people still didn't show up at the booths.
All of this said, how could we boost voter turnout? Beyond the current efforts to beef up social media safeguards against bots and fake news, as well as political calls to support less "Establishment"-tied figures, perhaps we could amend the law and hold elections during the spring. You know, that time of year when the holidays are not only out of the way, but flu season and gloom season are as well.
When 19th-century lawmakers originally decided to make the first Tuesday in November Election Day, they did so to ensure farmers — much of the make-up of the then-citizenry was agrarian — would have a window of time before winter to vote. Much has changed in the last 173 years, however, in terms of demographics. If all votes matter, and if we're genuinely interested in maximizing turnout, then we should, much like the lawmakers of yestercenturies, consider better timing.
Join Radiolab's Latif Nasser at 1pm ET today as he chats with Malcolm Gladwell live on Big Think.
Astronomers find these five chapters to be a handy way of conceiving the universe's incredibly long lifespan.
- We're in the middle, or thereabouts, of the universe's Stelliferous era.
- If you think there's a lot going on out there now, the first era's drama makes things these days look pretty calm.
- Scientists attempt to understand the past and present by bringing together the last couple of centuries' major schools of thought.
The 5 eras of the universe<p>There are many ways to consider and discuss the past, present, and future of the universe, but one in particular has caught the fancy of many astronomers. First published in 1999 in their book <a href="https://amzn.to/2wFQLiL" target="_blank"><em>The Five Ages of the Universe: Inside the Physics of Eternity</em></a>, <a href="https://en.wikipedia.org/wiki/Fred_Adams" target="_blank">Fred Adams</a> and <a href="https://en.wikipedia.org/wiki/Gregory_P._Laughlin" target="_blank">Gregory Laughlin</a> divided the universe's life story into five eras:</p><ul><li>Primordial era</li><li>Stellferous era</li><li>Degenerate era</li><li>Black Hole Era</li><li>Dark era</li></ul><p>The book was last updated according to current scientific understandings in 2013.</p><p>It's worth noting that not everyone is a subscriber to the book's structure. Popular astrophysics writer <a href="https://www.forbes.com/sites/ethansiegel/#30921c93683e" target="_blank">Ethan C. Siegel</a>, for example, published an article on <a href="https://www.forbes.com/sites/startswithabang/2019/07/26/we-have-already-entered-the-sixth-and-final-era-of-our-universe/#7072d52d4e5d" target="_blank"><em>Medium</em></a> last June called "We Have Already Entered The Sixth And Final Era Of Our Universe." Nonetheless, many astronomers find the quintet a useful way of discuss such an extraordinarily vast amount of time.</p>
The Primordial era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEyMi9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYyNjEzMjY1OX0.PRpvAoa99qwsDNprDme9tBWDim6mS7Mjx6IwF60fSN8/img.jpg?width=980" id="db4eb" class="rm-shortcode" data-rm-shortcode-id="0e568b0cc12ed624bb8d7e5ff45882bd" data-rm-shortcode-name="rebelmouse-image" />
Image source: Sagittarius Production/Shutterstock<p> This is where the universe begins, though what came before it and where it came from are certainly still up for discussion. It begins at the Big Bang about 13.8 billion years ago. </p><p> For the first little, and we mean <em>very</em> little, bit of time, spacetime and the laws of physics are thought not yet to have existed. That weird, unknowable interval is the <a href="https://www.universeadventure.org/eras/era1-plankepoch.htm" target="_blank">Planck Epoch</a> that lasted for 10<sup>-44</sup> seconds, or 10 million of a trillion of a trillion of a trillionth of a second. Much of what we currently believe about the Planck Epoch eras is theoretical, based largely on a hybrid of general-relativity and quantum theories called quantum gravity. And it's all subject to revision. </p><p> That having been said, within a second after the Big Bang finished Big Banging, inflation began, a sudden ballooning of the universe into 100 trillion trillion times its original size. </p><p> Within minutes, the plasma began cooling, and subatomic particles began to form and stick together. In the 20 minutes after the Big Bang, atoms started forming in the super-hot, fusion-fired universe. Cooling proceeded apace, leaving us with a universe containing mostly 75% hydrogen and 25% helium, similar to that we see in the Sun today. Electrons gobbled up photons, leaving the universe opaque. </p><p> About 380,000 years after the Big Bang, the universe had cooled enough that the first stable atoms capable of surviving began forming. With electrons thus occupied in atoms, photons were released as the background glow that astronomers detect today as cosmic background radiation. </p><p> Inflation is believed to have happened due to the remarkable overall consistency astronomers measure in cosmic background radiation. Astronomer <a href="https://www.youtube.com/watch?v=IGCVTSQw7WU" target="_blank">Phil Plait</a> suggests that inflation was like pulling on a bedsheet, suddenly pulling the universe's energy smooth. The smaller irregularities that survived eventually enlarged, pooling in denser areas of energy that served as seeds for star formation—their gravity pulled in dark matter and matter that eventually coalesced into the first stars. </p>
The Stelliferous era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTEzNy9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxMjA0OTcwMn0.GVCCFbBSsPdA1kciHivFfWlegOfKfXUfEtFKEF3otQg/img.jpg?width=980" id="bc650" class="rm-shortcode" data-rm-shortcode-id="c8f86bf160ecdea6b330f818447393cd" data-rm-shortcode-name="rebelmouse-image" />
Image source: Casey Horner/unsplash<p>The era we know, the age of stars, in which most matter existing in the universe takes the form of stars and galaxies during this active period. </p><p>A star is formed when a gas pocket becomes denser and denser until it, and matter nearby, collapse in on itself, producing enough heat to trigger nuclear fusion in its core, the source of most of the universe's energy now. The first stars were immense, eventually exploding as supernovas, forming many more, smaller stars. These coalesced, thanks to gravity, into galaxies.</p><p>One axiom of the Stelliferous era is that the bigger the star, the more quickly it burns through its energy, and then dies, typically in just a couple of million years. Smaller stars that consume energy more slowly stay active longer. In any event, stars — and galaxies — are coming and going all the time in this era, burning out and colliding.</p><p>Scientists predict that our Milky Way galaxy, for example, will crash into and combine with the neighboring Andromeda galaxy in about 4 billion years to form a new one astronomers are calling the Milkomeda galaxy.</p><p>Our solar system may actually survive that merger, amazingly, but don't get too complacent. About a billion years later, the Sun will start running out of hydrogen and begin enlarging into its red giant phase, eventually subsuming Earth and its companions, before shrining down to a white dwarf star.</p>
The Degenerate era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE1MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYxNTk3NDQyN30.gy4__ALBQrdbdm-byW5gQoaGNvFTuxP5KLYxEMBImNc/img.jpg?width=980" id="77f72" class="rm-shortcode" data-rm-shortcode-id="08bb56ea9fde2cee02d63ed472d79ca3" data-rm-shortcode-name="rebelmouse-image" />
Image source: Diego Barucco/Shutterstock/Big Think<p>Next up is the Degenerate era, which will begin about 1 quintillion years after the Big Bang, and last until 1 duodecillion after it. This is the period during which the remains of stars we see today will dominate the universe. Were we to look up — we'll assuredly be outta here long before then — we'd see a much darker sky with just a handful of dim pinpoints of light remaining: <a href="https://earthsky.org/space/evaporating-giant-exoplanet-white-dwarf-star" target="_blank">white dwarfs</a>, <a href="https://earthsky.org/space/new-observations-where-stars-end-and-brown-dwarfs-begin" target="_blank">brown dwarfs</a>, and <a href="https://earthsky.org/astronomy-essentials/definition-what-is-a-neutron-star" target="_blank">neutron stars</a>. These"degenerate stars" are much cooler and less light-emitting than what we see up there now. Occasionally, star corpses will pair off into orbital death spirals that result in a brief flash of energy as they collide, and their combined mass may become low-wattage stars that will last for a little while in cosmic-timescale terms. But mostly the skies will be be bereft of light in the visible spectrum.</p><p>During this era, small brown dwarfs will wind up holding most of the available hydrogen, and black holes will grow and grow and grow, fed on stellar remains. With so little hydrogen around for the formation of new stars, the universe will grow duller and duller, colder and colder.</p><p>And then the protons, having been around since the beginning of the universe will start dying off, dissolving matter, leaving behind a universe of subatomic particles, unclaimed radiation…and black holes.</p>
The Black Hole era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE2MS9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYzMjE0OTQ2MX0.ifwOQJgU0uItiSRg9z8IxFD9jmfXlfrw6Jc1y-22FuQ/img.jpg?width=980" id="103ea" class="rm-shortcode" data-rm-shortcode-id="f0e6a71dacf95ee780dd7a1eadde288d" data-rm-shortcode-name="rebelmouse-image" />
Image source: Vadim Sadovski/Shutterstock/Big Think<p> For a considerable length of time, black holes will dominate the universe, pulling in what mass and energy still remain. </p><p> Eventually, though, black holes evaporate, albeit super-slowly, leaking small bits of their contents as they do. Plait estimates that a small black hole 50 times the mass of the sun would take about 10<sup>68</sup> years to dissipate. A massive one? A 1 followed by 92 zeros. </p><p> When a black hole finally drips to its last drop, a small pop of light occurs letting out some of the only remaining energy in the universe. At that point, at 10<sup>92</sup>, the universe will be pretty much history, containing only low-energy, very weak subatomic particles and photons. </p>
The Dark Era<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yMjkwMTE5NC9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTY0Mzg5OTEyMH0.AwiPRGJlGIcQjjSoRLi6V3g5klRYtxQJIpHFgZdZkuo/img.jpg?width=980" id="60c77" class="rm-shortcode" data-rm-shortcode-id="7a857fb7f0d85cf4a248dbb3350a6e1c" data-rm-shortcode-name="rebelmouse-image" />
Image source: Big Think<p>We can sum this up pretty easily. Lights out. Forever.</p>
UNC School of Medicine researchers identified the amino acid responsible for the trip.
- Researchers at UNC's School of Medicine have discovered the protein responsible for LSD's psychedelic effects.
- A single amino acid—part of the protein, Gαq—activates the mind-bending experience.
- The researchers hope this identification helps shape depression treatment.
What is Bicycle Day?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="d346092205da3c9ed10bad283222c9f1"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/L32mAiLXnLs?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Back in the world of clinical science, LSD has always showed promise. That trend continues as restrictions are finally easing up. Understanding LSD's effects on our brain's complex system of networks is an important step toward discovering therapeutic actions. As Roth <a href="https://www.inverse.com/mind-body/how-lsd-binds-to-the-brain-study" target="_blank">says</a> of his research,</p><p style="margin-left: 20px;">"Now we know how psychedelic drugs work – finally! Now we can use this information to, hopefully, discover better medications for many psychiatric diseases."</p><p>Using X-ray crystallography, Roth's team discovered a single amino acid—a building block of the protein, Gαq—responsible for binding to serotonin receptors. As LSD is only a partial agonist, they also experimented with a full-agonist designer psychedelic in order to observe complete receptor activation. This amino acid appears to be the master switch for the psychedelic experience. </p><p>While psilocybin has been in the news, the psychedelic renaissance is expanding in all directions. Phase 1 clinical trials on the <a href="https://newatlas.com/science/landmark-clinical-trial-lsd-mdma-mindmed/" target="_blank">combination</a> of LSD, MDMA, and psychotherapy will soon commence. LSD's effects on <a href="https://clinicaltrials.gov/ct2/show/NCT03866252" target="_blank" rel="noopener noreferrer">Major Depressive Disorder</a> and <a href="https://www.sciencealert.com/first-clinical-trial-shows-micro-doses-of-lsd-can-increase-a-person-s-pain-tolerance" target="_blank">pain management</a> are ongoing. With the <a href="https://www.bloomberg.com/news/articles/2020-09-18/-magic-mushroom-company-moves-toward-mainstream-in-nasdaq-ipo" target="_blank" rel="noopener noreferrer">first psychedelics company</a> to IPO on the American stock market, along with hundreds of millions of dollars of investment flowing into similar companies and organizations, the push for legalized psychedelics intensifies. </p>
Credit: ynsga / Shutterstock<p>Researchers are actively attempting to remove the hallucinogenic component of psychedelics for widespread therapeutic usage—<a href="https://www.healtheuropa.eu/could-ibogaine-offer-a-revolutionary-long-term-solution-to-addiction/100635/" target="_blank">trials</a> using ibogaine for addiction treatment, for example. Identifying the chemical effects of psychedelics on our brains is an essential step in that process.</p><p>Of course, believing psychedelics <em>only</em> matters to brain chemistry is problematic as well. The rituals associated with their use are just as relevant. The "<a href="https://en.wikipedia.org/wiki/Set_and_setting" target="_blank">set and setting</a>" model espoused by Timothy Leary reminds us that biology isn't everything; environmental factors play just as important a role in mental health. </p><p>Isolating specific chemicals without understanding the impact of the drug <em>and</em> the environment overlooks the holistic nature of the psychedelic experience. For example, ketamine trials <a href="https://bigthink.com/surprising-science/ketamine-depression" target="_self">were rushed</a> and could potentially backfire; we can't afford to make that mistake again. </p><p>Still, understanding the pathways LSD utilizes is an important step forward. As Roth says, "Our ultimate goal is to see if we can discover medications which are effective, like psilocybin, for depression but do not have the intense psychedelic actions." In a world where more people are growing anxious and depressed by the day, every intervention should be explored.</p><p> --</p><p><em>Stay in touch with Derek on <a href="http://www.twitter.com/derekberes" target="_blank">Twitter</a>, <a href="https://www.facebook.com/DerekBeresdotcom" target="_blank" rel="noopener noreferrer">Facebook</a> and <a href="https://derekberes.substack.com/" target="_blank" rel="noopener noreferrer">Substack</a>. His next book is</em> "<em>Hero's Dose: The Case For Psychedelics in Ritual and Therapy."</em></p>
A team of researchers have discovered the brain rhythmic activity that can split us from reality.
- Researchers have identified the key rhythmic brain activity that triggers a bizarre experience called dissociation in which people can feel detached from their identity and environment.
- This phenomena is experienced by about 2 percent to 10 percent of the population. Nearly 3 out of 4 individuals who have experienced a traumatic event will slip into a dissociative state either during the event or sometime after.
- The findings implicate a specific protein in a certain set of cells as key to the feeling of dissociation, and it could lead to better-targeted therapies for conditions in which dissociation can occur.
What is dissociation?<span style="display:block;position:relative;padding-top:56.25%;" class="rm-shortcode" data-rm-shortcode-id="bd2f1f29418bd4805bf1282001dca814"><iframe type="lazy-iframe" data-runner-src="https://www.youtube.com/embed/XF2zeOdE5GY?rel=0" width="100%" height="auto" frameborder="0" scrolling="no" style="position:absolute;top:0;left:0;width:100%;height:100%;"></iframe></span><p>Dissociation is an experience commonly described as a feeling of sudden detachment from the individual's identity and environment, almost like an out-of-body experience. This mysterious phenomena is experienced by about 2 percent to 10 percent of the population.</p><p>"This state often manifests as the perception of being on the outside looking in at the cockpit of the plane that's your body or mind — and what you're seeing you just don't consider to be yourself," explained senior author Karl Deisseroth, MD, PhD, <a href="https://med.stanford.edu/news/all-news/2020/09/researchers-pinpoint-brain-circuitry-underlying-dissociation.html" target="_blank" rel="noopener noreferrer">in a Stanford Medicine news release</a>. Deisseroth is a professor of bioengineering and of psychiatry and behavioral sciences, as well as a Howard Hughes Medical Institute investigator.</p><p>Nearly three-quarters of individuals who have experienced a traumatic event will slip into a dissociative state either during the event or in the hours or even weeks that follow, according to Deisseroth. Most of the time, the dissociative experiences end on their own within a few weeks of the trauma. But the eerie experience can become chronic, such as in cases of post-traumatic stress disorder, and extremely disruptive in daily life. The state of dissociation can also occur in epilepsy and be invoked by certain drugs. </p><p>Until now, no one has known what exactly is going on inside the brain triggering and sustaining the feeling of dissociation — and so it has been a challenge to figure out how to stop it and develop effective treatments. </p>
New Research: The Molecular Underpinnings of Dissociation<img type="lazy-image" data-runner-src="https://assets.rebelmouse.io/eyJhbGciOiJIUzI1NiIsInR5cCI6IkpXVCJ9.eyJpbWFnZSI6Imh0dHBzOi8vYXNzZXRzLnJibC5tcy8yNDQyNjk3My9vcmlnaW4uanBnIiwiZXhwaXJlc19hdCI6MTYwNTQ3MTI1NX0._nJoxm1eDcTsHsy1Y27JxNl2uR5hlbEYDWYoQlO0EAU/img.jpg?width=1245&coordinates=0%2C121%2C0%2C121&height=700" id="26e86" class="rm-shortcode" data-rm-shortcode-id="1094af23e35a498a8a6b691f1d0cbfaf" data-rm-shortcode-name="rebelmouse-image" alt="neurons" />
Neurons from a mouse spinal cord
Credit: NICHD on Flickr<p>Last week, in a study published in <a href="https://www.nature.com/articles/s41586-020-2731-9" target="_blank">Nature</a><a href="https://www.nature.com/articles/s41586-020-2731-9">,</a> Deisseroth and his colleagues at Stanford University uncovered a localized brain rhythm and molecule that underlies this state.</p><p>"This study has identified brain circuitry that plays a role in a well-defined subjective experience," said Deisseroth. "Beyond its potential medical implications, it gets at the question, 'What is the self?' That's a big one in law and literature, and important even for our own introspections."</p><p>The authors' findings implicate a specific protein existing in a particular set of cells as key to the feeling of dissociation. </p><p>The research team first used a technique called widefield calcium imaging to record brain-wide neuronal activity in lab mice. They observed and analyzed changes in those brain rhythms after the animals had been administered a range of drugs that are known to cause dissociative states: ketamine, phencyclidine (PCP), and dizocilpine (MK801). At a certain dosage of ketamine, the mice behaved in a way that suggested that they were likely experiencing dissociation. For example, when the animals were placed on an uncomfortably warm surface, they reacted to it by flicking their paws. However, they signaled that they didn't care enough about the unpleasantness to do what they would typically do in such a situation, which is to lick their paws to cool them off. This suggested a dissociation from the surrounding environment.</p><p>The drug produced oscillations in neuronal activity in a region of the mices' brain called the retrosplenial cortex, an area essential for various cognitive functions such as navigation and episodic memory (a unique memory of a specific event). The oscillations occurred at about 1-3 hertz (three cycles per second). The authors then examined the active cells in more detail by using two-photon imaging for higher resolution. This revealed that the oscillations were occurring only in layer 5 of the retrosplenial cortex. Next, the researchers recorded neuronal activity across other regions of the brain. </p><p>"Normally, other parts of the cortex and subcortex are functionally connected to neuronal activity in the retrosplenial cortex," Ken Solt and Oluwaseun Akeju wrote in <a href="https://www.nature.com/articles/d41586-020-02505-z#ref-CR1" target="_blank">Nature</a>. "However, ketamine caused a disconnect, such that many of these brain regions no longer communicated with the retrosplenial cortex."</p><p>The scientists then used optogenetics, a method of manipulating living tissue with light to control neural function, to stimulate neurons in the mice's retrosplenial cortex. When the scientists did this at a 2-hertz rhythm, they were able to cause dissociative behavior in the animals analogous to the behavior caused by ketamine without using drugs. The experiments conducted by the team displayed how a particular type of protein, an ion channel, was essential to the generation of the hertz signal that caused the dissociative behavior in mice. Scientists are hopeful that this protein could be a potential treatment target in the future. </p>