For many of us, the holiday season entails giving and receiving gifts. If you were on the receiving end, I invite you to reflect on how any gifts given to you made you feel in light of the findings of a recent line of research, soon to be published in the Journal of Consumer Research. And if you were on the giving end, I invite you to reflect on how any gifts given by you made the recipients feel.
In a series of studies, Kimberlee Weaver and her colleagues showed that recipients appreciated an expensive gift more than the same expensive gift when coupled with a less expensive one.
Makes little sense, right? More should be better, especially in a materialistic world.
But these researchers showed that gift-givers evaluate the worth and impact of what they give by adding up the worth and impact of individual gifts, whereas gift-receivers evaluate what they get as a whole, in effect averaging together the worth and impact of the individual gifts. On average, an expensive gift and a modest gift are less impressive than the expensive gift alone. They dubbed this phenomenon the presenter’s paradox, and it provides food for thought and not just about literal gifts.
Recipients and presenters apparently have different mindsets, and they may not understand the perspective of the other. Weaver and colleagues discussed the implications of their research with respect to law, negotiation, and public policy.
As a college teacher, the holiday season for me always coincides with the end of the fall semester, when I talk to students who did not do as well as they wished in classes I teach. They usually offer explanations, which I take seriously, but the more explanations a student offers, the more likely I am to hear them as mere excuses. One good explanation is enough and certainly better than a good one followed by two or three not-so-good ones!
On a more positive note, consider how we savor positive events of all sorts, not just holiday gifts. Suppose more than one good thing happens at a time? Hooray for us, but do we average them together or sum them? The research by Weaver and her colleagues suggests that we would be better served by summing up their impacts. That may be difficult to do, so a more practical suggestion – one that squares with research on savoring – is to experience one positive event at a time and not get distracted by others.
Reference: Weaver, K., Garcia, S. M., & Schwarz, N. (in press). The presenter’s paradox. Journal of Consumer Research.
Why we pay attention to what we are eating, but not how much.
He thought, “this has a lot of calories, I really shouldn’t eat it.” It was a rich, creamy serving of ice-cream and he was already pretty full.
So he added some chopped nuts and strawberries. Somehow convinced that it now had fewer calories, and guilt free, he dug in.
Only a twisted mind would think you can decrease calories by adding more. So I guess I have a twisted mind, because “he” is me. I laugh about it, but my attitude has a lot to do with the epidemic of obesity in this country.
Is it only twisted minds that do this, though? Or do we all do it? Let’s look at some data.
Chernev (2011) asked people to estimate the number of calories in various meals, including a cheesesteak condition (yum).
There were two conditions:
• Unhealthy alone — for example a cheesesteak sandwich. • Unhealthy plus healthy — for example the same cheesesteak sandwich plus a side of healthy vegetables.
Calorie ratings were higher for the unhealthy meal alone. Adding the healthy side made the meal seem to have fewer calories. In other words, x + 1 is less than x. Chernev (2011) called it the dieter’s paradox.
There was more. Weight conscious individuals were especially likely to show this effect. They thought the carrots and celery decreased calories by a lot, which is surprising if you assume they’d be most tuned in about estimating calories.
This study, and my ice-cream consumption, is an example of scope neglect. When we make judgments we aren’t very good at paying to attention to how big something is. Another example is that people will pay about the same amount to save 2,000 birds as to save 200,000 (Desvouges et al., 1993).
The dieter’s paradox is fundamental to the obesity epidemic in America. We pay attention to what we eat but not how much. When we look at the French, with their rich food, we wonder why they aren’t overweight. When we look at ourselves, with our huge servings that (sometimes) aren’t as calorie-dense, we wonder why we are overweight. That’s like wondering why ice cream alone has fewer calories than ice-cream with nuts and fruit on it.
References: (1) Chernev, A. (2011). The Dieter’s Paradox. Journal of Consumer Psychology, 21, 178–183. doi:10.1016/j.jcps.2010.08.002 (2) Desvouges, W.H., Johnson, F., Dunford, R., Hudson, S., Wilson, K., and Boyle, K. 1993. Measuring resource damages with contingent valuation: Tests of validity and reliability, in: Contingent Valuation: A Critical Assessment. Amsterdam: North Holland.
Consider the paradox of the end: we set ourselves a goal and make great efforts to achieve it. Doing so is often strenuous, but gives life direction, purpose and meaning. We see the goal as valuable, and this gives us a purpose and endows meaning on the means used to achieve this goal. But then, a short while after we achieve the goal, we frequently sense, paradoxically, that meaning in our life is diminished rather than enhanced. A sense of emptiness sets in. We are surprised to find that in achieving the end we lost the meaning we had while striving. Oddly, we are kind of sorry that we accomplished the end. To sense meaning again we quickly set to ourselves another end. But once achieved it, too, loses its meaning, and we pick yet another. It appears that the ends or goals are not really valuable; they are just excuses to strive for something.
However, if the goals are not really meaningful, then our efforts to achieve them are, in fact, also not meaningful. And this suggests that much of what we do is actually pointless. Since most of the value in our lives has to do with ends and efforts to achieve them, the paradox of the end makes life meaningless. When we treat our endeavors in life as meaningful we are just pretending to ourselves that our ends and the efforts to achieve them are of value. If we consider it sincerely, this argument for the meaninglessness of life claims, we have to accept the worthlessness of our ends, and therefore also the worthlessness of the means to attain them, and hence also the meaninglessness of life.
The paradox of the end has been often acknowledged (even if usually not by this name). For example, Oscar Wilde claimed “In this world there are only two tragedies. One is not getting what one wants, and the other is getting it. … The last is a real tragedy.” Likewise, The important pessimist philosopher Arthur Schopenhauer elaborated on the paradox and claimed that it is part of what makes life bad and meaningless.
But do we really have here a good argument against the meaning of life? I do not think so. Here are four reasons why.
First, as already argued by Oswald Hanfling, it is simply wrong that the meaning of all attained ends completely vanishes. Most people continue to see many achieved ends as highly valuable even years after attaining them. True, elation is often most intense in the first hours or days. However, most people recognize the value in having found love, won a prize, finished college, succeeded at work, or solved a personal problem even decades after accomplishing these ends. Thus, for most people, the empirical claim at the basis of the argument is incorrect.
Second, some achieved ends have no terminus. For example, being and remaining a loving and supportive husband, a good teacher, or a decent person are goals people attain every day and never cease accomplishing. The paradox does not apply at all to such unfinished ends. This also holds for regulative ends, that is, ends people know they will never achieve fully but towards which they aim and direct themselves. Such are, for example, attempts to develop a deeper understanding of music, enhance a capability, be more moral, or come nearer to God. Since such aims are never achieved, the paradox of the end does not apply to them.
Third, many meaningful aspects of life do not at all have to do with efforts to achieve ends; some meaningful aspects of life are not even intended, but just happen. For example, we may just find ourselves having a deep insight or realization, a strong aesthetic experience, a significant human encounter, or an intense religious involvement.
Fourth, this argument for the meaninglessness of life ignores people’s ability to change the degree to which they experience achieved ends as meaningless. Sensing the paradox of the end is often related to specific psychological tendencies that, when radicalized, become problematic, but with the right effort and counseling can often be moderated. For example, the paradox frequently coincides with Workaholism. Those inwardly compelled to work incessantly find it hard to just sit and enjoy their achievements, since their urge to continue working makes them restless. Likewise, overcompetitive people find it hard to feel satisfied for a long time after attaining a goal since they quickly sense an urge to embark on another competitive endeavor, and cannot but compare their achievement to some better one someone else has attained. Further, some people cannot just enjoy what they have achieved, feeling an urge to “go on and do something,” simply because they are nervous. But these and similar dynamics do not show that our achievements lack real value or that life is meaningless. They only show that some people’s temperamental habits diminish their ability to appreciate attained value. Practice and treatment can moderate many of these temperamental habits.
The paradox of the end does capture something about certain human experiences, but does not show or make life meaningless. In moderate form, it may actuality be beneficial, leading us to seek further valuable goals to pursue.
References: (1) Oscar Wilde, Lady Windermere’s Fan III, in Complete Works of Oscar Wilde (London: Collins, 1966, 417. (2) Arthur Schopenhauer, The World as Will and Representation, trans. E. F. J. Payne, vols. 1–2 (New York: Dover, 1969), 1:312-314. (3) Oswald Hanfling, The Quest for Meaning (New York: Blackwell, 1988), 7.
This article is republished here from psychology today under common creative licenses.
Does the moon still exist when you’re not looking at it? In a provocative new book titled The Case Against Reality: Why Evolution Hid the Truth from Our Eyes, psychologist Donald Hoffman suggests that the answer is no. Evolution, the argument goes, may have shaped our perceptions to create an interface analogous to a computer desktop interface. Trains, snakes, and even the moon may be mere icons that guide our behavior, much like the icons on your computer desktop. That doesn’t mean that they don’t represent something real out there—just as dragging a blue email icon to your trash really does delete an email file in your computer, stepping in front of a train really does kill you. But, Hoffman argues, just as the email file in your computer is not actually a blue pixelated rectangle, the actual threat posed by the train is not actually a large, elongated object occupying three dimensions of space and one of time. We must take the train seriously, but not necessarily literally, his reasoning goes.
Indeed, just as direct access to the bits and voltages inside a computer would be unlikely to help us quickly write an email, Hoffman claims that direct access to the complex information in our real environment is unlikely to help us pass our genes to the next generation. With playful references to The Matrix (“There is no spoon …”), Hoffman argues that perceptions that are veridical—that is, truthfully reflecting objective reality—are less likely to help us survive and raise offspring than false perceptions. Hoffman argues that false or non-veridical perceptions actually serve as an interface, compressing vast amounts of information to help us survive.
The basis of this claim lies in evolutionary game theory, simulations that show how creatures survive based on whether or not their perceptions are veridical. Using these simulations, Hoffman and several collaborators have put forth a mathematical argument that there is virtually zero probability that our perceptions are a true or even almost-true reflection of reality. As a concrete example, consider an organism that can only survive in an environment with an intermediate concentration of some particular substance. Perhaps this substance is oxygen: high and low concentrations are lethal, so our organism must find the sweet spot in the middle. As argued in Chapter 4 of the book, if the organism directly sees the concentration of oxygen, then it will probably move towards the highest concentration and die. But if it instead only sees intermediate levels of oxygen, while being blind to high levels, then it can survive by moving only towards what it can see.
While the logic of this argument is rooted in evolution, Hoffman also invites us to consider some curious features of modern physics that also suggest that our perceptions are an interface. For instance, quantum mechanics, which governs the world at the atomic and subatomic scales, shows us that particles may not actually exist in a definite location until they are directly observed. You might think of this like a video game that only renders the visual graphics needed by the observer at any given moment. So, could quantum mechanics also suggest that our perceptions exist only to compress a far more complex reality?
Like Morpheus from the Matrix, Hoffman offers us a red pill with the promise of understanding the truth about the outside world. Yet, as the reader, Joel Frohlich, co-editor-in-chief of Knowing Neurons, found this red pill difficult to swallow. Occam’s razor, a principle for choosing between competing scientific theories, tells us to select the simplest theory with the fewest parts. Isn’t the simpler theory that our perceptions are more or less true, rather than a mere interface hiding a higher dimensional reality? He said he was lucky enough to interview Hoffman and raise this objection to him; an abbreviated transcript of their conversation follows this book review.
In both their conversation and in the book, Hoffman argues that his interface theory of perception (ITP) is needed to address the gap between physical processes that take place in the brain and our conscious experiences. Even if we fully understand the neurophysiology of color perception, why, for example, does it feel like something to behold a rainbow? Why don’t the neurological processes that allow the brain to perceive color simply take place in the dark, so to speak, without subjective experience? This conundrum, known as the hard problem of consciousness, has baffled many scientists and philosophers. Hoffman believes the way forward is to assume that consciousness precedes brains and is fundamental, and that reality is, at the most basic level, a network of interacting conscious agents.
Whether or not you agree with ITP or Hoffman’s network of conscious agents theory, The Case Against Reality is not only a highly enjoyable read but also a stimulating exercise that challenges us to consider how true our perceptions really are. Nearly all neuroscientists agree that even if our perceptions are largely veridical, we don’t always see the truth. Illusions like the Necker Cube, for instance, show that our minds can be tricked into perceiving things that aren’t there. In the image below, is the cream side the far or the near side of the cube? Looking at the cube, you can willfully cause it to flip between both orientations.
The Necker Cube has no true orientation, only that which exists in the mind. Neuroscientists like Anil Seth at the University of Sussex have used such illusions to argue that all our perceptions are hallucinations based on what our brains predict to be true. That is to say, what we see is not merely the light that hits our retina, but a far more user-generated experience, if you will, based on predictions such as “faces are always convex and never concave.” In that particular example, we know faces in our environment nearly always curve outward, but the occasional exception may result in a powerful illusion. While Seth believes that the predictions that drive our perceptions are usually true, Hoffman diverges in his thinking by arguing that space and time are themselves only an interface that exists in the human mind. Although Joel more in agreement with Seth, there’s no doubt that many of the brain’s predictions regarding color, motion, and orientation are sometimes off the mark. With new illusions being discovered each year, the exact extent to which our wakeful, sober perceptions are veridical may remain an open question for years to come.
In an interview carried out by psychology today with the author, Donald Hoffman they asked:
How long have you had this intuition about reality?
Donald Hoffman replied, “I first had the intuition in 1986. I was working with Chetan Prakash and Bruce Bennett on a mathematical model of perception. And it was looking at the mathematics of that model and having a conversation with them about it that I remember one day I suddenly realized that what we’re seeing might not be real, that we might just be making this all up. And it hit me all the harder because it was my own theory. And I hadn’t been trying to build it into the theory, I was just trying to build a mathematical model of perception”.
That was the red pill moment for you?
That’s right, the mathematics opened up the red pill and handed it to me. I still remember—I was so stunned I had to sit down.
Do you see your theory of conscious agents as a solution to the hard problem of consciousness?
Yes, that’s why I’m proposing it. I’ve been prompted by how little progress we’ve made in physicalist approaches to the hard problem of consciousness. You know, integrated information theory, microtubule theory, global workspace theory, and so forth can’t explain a single conscious experience.
I think I have difficulty accepting ITP because Occam’s razor suggests that, all other things being equal, we should favor the simplest hypothesis. Doesn’t Occam’s razor favor the hypothesis that objective reality is more or less what we see, rather than something beyond three dimensions of space and one of time?
Well, I would agree with you and I would have been happy to go that direction if we could solve the hard problem of consciousness from within that physicalist framework. It’s the utter failure to solve the hard problem of consciousness that’s sort of forced my hand here. And I mean, I could have had ITP and just say, well, there’s a more complicated physical universe. Maybe there are ten dimensions instead of just three spatial and one temporal. I could have done something like that. But Occam’s Razor is about theories that can explain the phenomena, right? Of all the theories that can explain the phenomena, choose the simplest. Well, that theory, that we’re seeing reality as it is, cannot explain the most critical phenomena that we have, namely our conscious experiences. So, Occam’s Razor fails to apply here because Occam’s Razor is only about theories that can do the explanatory work. Now you’re choosing among them. Well, physicalism utterly fails to explain anything about consciousness. It just can’t do it.
If we only perceive fitness payoffs, why can I see the Milky Way Galaxy under a dark sky at night? I don’t see any obvious fitness payoff there.
Right. So the idea will be that evolution has shaped us with a very simplified interface that’s been shaped mostly to report the stuff that’s going to keep us alive. But if you look up at the stars, you’ll notice that you’ll see you see a mountain in the distance and then you see the moon and the stars coming up behind the mountain. The mountain looks far away. And the stars and the moon look a little bit further away. But, not that much further.
Right, you have no intuition for how far they are.
No intuition. And that’s why we believed for a long time that there was this little shell around the earth and things weren’t that far away. And that actually is an interesting aspect of the interface idea. And that is, what is space from the point of view of the interface theory? Well, it’s just a data structure. Space and time are just a data structure. They’re there to represent fitness payoffs. The distance from me to an apple, say, here like two meters away versus another apple, you know, 20 meters away—that distance is coding the percentage of my caloric resources that I currently have that would be required to be expended to get the resources in the apple at two meters versus 20 meters. In other words, distance is a calorie expenditure representing fitness cost. And so, it’s no surprise that the stars look about as far away as the mountain, because they’re both at infinity given my caloric resources.
In your book, you talk a lot about visual illusions like the Necker Cube. What about hallucinations? Do you think there’s any possibility that hallucinations might be more veridical than our sober perceptions?
Not the normal hallucinations if you get DT—delirium tremens1—or something like that. Yeah, those are probably not going to be any more veridical.
What about Aldous Huxley’s idea expressed in The Doors of Perception, that our conscious mind filters sensory input and that psychedelic drugs release this filter on reality?
I am absolutely open to the idea, that there could be [drugs] like DMT2 opening us up to new levels of reality that are genuine insights.
The way that people describe DMT, that almost sounds like something outside of spacetime, right?
That’s right, and people who’ve done those [DMT] come back saying that it felt more real than our everyday reality. They end up being more convinced that it’s real. They’re interacting with these guides that are actually telling them relevant stuff that’s important to them, and every time they go back on another trip, they pick up where they left off and are learning new stuff. I mean, that doesn’t sound like the musing of a mind addled by alcohol. I’m not saying I’m sure, but I can’t dismiss the possibility that, in some sense, as Huxley puts it, we’ve opened the doors of perception, or as James puts it, this filmiest of screens, between us and other forms of conscious experience has been split, and we’re seeing these other forms of conscious experience that could be interface representations other than the one that we’ve got. On the other hand, it could also be that we just have addled brains.
What do you think of Anil Seth’s idea that we hallucinate our reality?
He likes the idea that we construct what we see. But he still assumes that in the normal case we are reconstructing some aspect of a physical reality. He’s a really bright guy. And a really nice guy. But the question is, what is controlling the hallucination? And he’s saying an objective physical reality that we need to track in order to stay alive and be fit. So it’s an objective reality that’s controlling the hallucination. And I’m saying that, no, all the stuff that we’re seeing, it’s a hallucination in the sense that it’s just a visualization tool that doesn’t resemble reality.
Quantum physics seems to suggest that subatomic particles don’t have a definite location in space until we observe them, almost as if we construct our own reality. Would you have come up with this idea if you didn’t know what you knew about quantum physics?
Oh, absolutely. It was entirely the theory of evolution by natural selection that sort of nailed down the ITP idea for me. I was aware of quantum theory in the 80s, so no doubt it influenced me. But I think I interpreted the quantum stuff the way most physicists interpret it, not in terms that space and time are just a user interface. So I was aware of the quantum weirdness, but I think it was my study of perception that really tipped me over to realizing that maybe spacetime itself is just a user interface. And then I could go back and look at the quantum stuff and realize, well, there is a way of interpreting the quantum stuff that’s compatible with the interface theory of perception.
Let’s talk about your idea that reality is, at the most fundamental level, a network of conscious agents. How do we get natural selection from there? If minds exist before genes, what is natural selection actually acting on?
So the idea is that reality is this vast social network of interacting conscious agents. And there is a sense of “fitness”, in vast social networks. The more connections you have, in some sense, the more fit you are. And the less connections you have, the less fit you are. So Google has tons of connections and the owners of Google are billionaires, Hoffman has a very few and he’s not a billionaire. And then you see this relationship between the number of social connections and fitness. What we may have to do is the following: we may have to say, OK, let’s look at evolution by natural selection. Let’s try to pull that back, do a reverse interface. Pull it back through the interface out to the realm of conscious agents. There’ll be a number of dynamics of conscious agents that are compatible with it. Let’s look at those dynamics and see which one makes sense. And then that will give us some insight into what’s going on in the realm of conscious agents, what they’re up to, and then when we project that back into our spacetime interface, we should get evolution by natural selection or hopefully a generalization that makes new predictions beyond evolution by natural selection. Same thing for quantum mechanics and general relativity.
Does ITP have spiritual implications?
I want a scientific spirituality in which we begin to explore a world beyond space and time. But we do it with mathematically precise models, and we start to address the big questions about why are we here and what is human consciousness about? Where did it come from? What’s the meaning of life? And so forth. Topics that scientists have in many cases said we don’t need to address. But in fact, they did address them. From the physicalist framework, the answer was, there is no life after death. There is no deep meaning to life, because once your brain dissolves, that’s it. And so they really did have a theory of life and transcendence: there is no such thing, there is no transcendence. But now all sorts of possibilities open up for exploration. And I’m pretty excited about it. So science and spirituality, I think, could really start to collaborate. But scientists have to let go of spacetime and spiritual traditions have to let go of dogmatism. Not easy.
The Case Against Reality: Why Evolution Hid the Truth from Our Eyes By Donald Hoffman 272 pages. W. W. Norton and Company.
References:  Hallucinations that result from alcohol withdrawal after excessive drinking.  N,N-dimethytrypatmine, a drug that causes powerful hallucinations and is an active ingredient ayahuasca, a brew made by the indigenous people of the Amazon basin. DMT is illegal in most countries.
Using new observational data from the space-based Solar Mass Ejection Imager and three different modeling techniques, astronomers have found that Betelgeuse, a red supergiant in the constellation of Orion, has a radius of about 764 solar radii, a mass between 16.5 and 19 solar masses, and is 548 light-years away.
“Betelgeuse has long fascinated scientists. But lately, it’s been behaving strangely,” said Dr. Meridith Joyce, an astronomer in the Research School of Astronomy and Astrophysics at the Australian National University and the ARC Centre of Excellence for All Sky Astrophysics in 3 Dimensions (ASTRO 3D).
“It’s normally one of the brightest stars in the sky, but we’ve observed two drops in the brightness of Betelgeuse since late 2019.”
“This prompted speculation it could be about to explode. But our study offers a different explanation.”
“We know the first dimming event involved a dust cloud. We found the second smaller event was likely due to the pulsations of the star.”
Dr. Joyce and colleagues were able to use hydrodynamic and seismic modeling to learn more about the physics driving the pulsations of Betelgeuse and get a clearer idea of what phase of its life this red supergiant is in.
“Our analysis confirmed that pressure waves — essentially, sound waves-were the cause of Betelgeuse’s pulsation,” said Dr. Shing-Chi Leung, an astronomer in the Walter Burke Institute for Theoretical Physics at Caltech.
“It’s burning helium in its core at the moment, which means it’s nowhere near exploding,” Dr. Joyce said.
“We could be looking at around 100,000 years before an explosion happens.”
“We also revealed how big Betelgeuse is, and its distance from Earth,” added Dr. László Molnár, an astronomer with the Konkoly Observatory.
“The actual physical size of Betelgeuse has been a bit of a mystery — earlier studies suggested it could be bigger than the orbit of Jupiter.”
“Our results say Betelgeuse only extends out to two thirds of that, with a radius 764 times the radius of the Sun.”
“Once we had the physical size of the star, we were able to determine the distance from Earth,” he said.
“Our results show it is 548 light-years from us — 25% closer than previous thought.”
The good news is Betelgeuse is still too far from Earth for the eventual explosion to have significant impact here.
“It’s still a really big deal when a supernova goes off. And this is our closest candidate. It gives us a rare opportunity to study what happens to stars like this before they explode,” Dr. Joyce said.
References: Meridith Joyce et al. 2020. Standing on the Shoulders of Giants: New Mass and Distance Estimates for Betelgeuse through Combined Evolutionary, Asteroseismic, and Hydrodynamic Simulations with MESA. ApJ 902, 63; doi: 10.3847/1538-4357/abb8db
Scientists have developed a new ‘Precision Medicine’ approach to treating the damaged DNA in the cancer cells of Pancreatic Cancer patients.
The findings mark an important step forward for potential treatment options for pancreatic cancer, improving the options and outcomes for a disease where survival rates have remained stubbornly low.
The study detailing the approach – led by the University of Glasgow and published in Gastroenterology – used cell lines and organoids that were generated from patients with pancreatic cancer to develop new molecular markers that can predict who will respond to drugs targeting DNA damage.
The researchers tested these markers using multiple drugs, and have developed a strategy that are now being taken forward into clinical trial. The trial will help doctors and researchers predict which patient will respond to which one of these drugs, either alone or in combination.
Funding for the trail has come from AstraZeneca and will now be included in the PRIMUS-004 clinical trial as part of the Precision-Panc therapeutic development platform for pancreatic cancer.
PRIMUS-004 is a ground-breaking pancreatic cancer trial, which aims to match patients with more targeted and effective treatment for their tumours. Run by Precision-Panc, a flagship therapeutic development programme dedicated to pancreatic cancer – led by the University of Glasgow with major funding from Cancer Research UK – the trial brings a precision medicine approach to pancreatic cancer treatment for the first time in the UK.
The trial will open for recruitment in Glasgow shortly, with 20 other centres throughout the UK to follow.
Although survival for many types of cancer has improved, pancreatic cancer survival has lagged significantly behind in the last 40 years. The disease is particularly hard to treat, partly because it’s often diagnosed at a late stage.
A major limitation to treating pancreatic cancer effectively is that there are very few treatment options for patients with the disease. Currently, some patients with pancreatic cancer cannot repair damaged DNA in the cancer cells, which makes the cancer vulnerable to some new and established drug treatments.
Dr David Chang, from the University of Glasgow’s Institute of Cancer Sciences, said: “Our study is a huge breakthrough in terms of what might be possible with future treatments. As part of our research, the strategy we’ve developed is extremely promising, and we’re very pleased and proud to see it now be taken into clinical trial. For us, this is a demonstration of a bench-to-bedside precision oncology approach to tackle this terrible disease.”
Michelle Mitchell, Cancer Research UK’s chief executive, said: “We urgently need new ways to treat pancreatic cancer. The disease only has a few treatment options and is generally diagnosed at a late stage, so survival has remained stubbornly low.
The Precision Panc study offers a dynamic way to explore new tailored treatments, and it’s fantastic that we now have new drug candidates to add to the PRIMUS-004 trial. We look forward to seeing if these drugs, which have shown promise in the lab, have the same impact for people with pancreatic cancer.”
Funding for PRIMUS 004 has been obtained from AstraZeneca and the study has been endorsed by Cancer Research UK. The trial is being coordinated by the Cancer Research UK Glasgow Clinical Trials Unit.
Researchers from Tokyo Metropolitan University studied the biodiversity of wetland plants over time in rice paddies in the Tone River basin, Japan. They found that paddies which were more likely to have been wetland before agricultural use retained more wetland plant species. On the other hand, land consolidation and agricultural abandonment were both found to negatively impact biodiversity. Their findings may one day inform conservation efforts and promote sustainable agriculture.
The Asian monsoon region is home to a vast number of rice paddies. Not only have they fed its billions of inhabitants for centuries, they are also an important part of the ecosystem, home to a vast array of wetland plant species. But as the population grows and more agricultural land is required, their sheer scale and complexity beg an important question: what is their environmental impact?
A team from Tokyo Metropolitan University led by Associate Professor Takeshi Osawa and their collaborators have been studying how rice paddies affect local plant life. In their most recent work, they investigated the biodiversity of wetland plants in rice paddies around the Tone River basin Japan. The Tone River is Japan’s second longest river, and runs through the 170,000 square kilometer expanse of the Kanto plains. Previous studies have looked at how a particular species or group of species fare in different conditions. Instead, the team turned their attention to the range of species that make up the plant community, with a particular focus on the number of wetland and non-wetland species present. Changes were tracked over time using extensive survey data from 2002, 2007 and 2012.
They found that not all rice paddies are equal when it comes to how well they support original wetland species. In fact, there was a correlation between how likely it was that the land was wetland before it was put to agricultural use, and the number of wetland species which were retained over time. Here, the team measured this using flow accumulation values (FAVs) for different plots of land, a simple metric which showed how easily water could accumulate. Importantly, this kind of approach might help us predict how amenable new rice paddies might be to the local wetland flora by calculating a simple number using the local terrain. However, they also found that things like land consolidation and agricultural abandonment could also have a negative impact. The emerging story is that both current human usage and original geographical conditions play an important role in deciding how ‘friendly’ rice paddies could be for the original wetland ecosystem.
The team believe that the same approach could be applied to different locations such as plantation forests which were (or were not) originally woodland. After all, many nations are turning to large scale tree planting to offset carbon emissions. The ability to systematically ‘assign’ how new land usage might impact local ecosystems is sure to greatly help restoration and conversation efforts.
Volume 11, Issue 30 of Oncotarget reported that previously, the authors showed that anti-estrogen drugs combined with a dendritic cell-based anti-HER-2 vaccine known to induce strong Th1-polarized immunity dramatically improved clinical response rates in patients with HER-2pos/ERpos early breast cancer.
Here, the Oncotarget authors show that the small molecule Akt antagonist MK-2206, when combined with the Th1 cytokines IFN-gamma and TNF-alpha, maximize indicators of apoptotic cell death in a panel of phenotypically-diverse human breast cancer lines.
These findings were mirrored by other, structurally-unrelated Akt-targeting drugs that work through different mechanisms. Interestingly, they found that MK-2206, as well as the other Akt antagonist drugs, also had a tendency to suppress Th1 cytokine expression in stimulated human and murine lymphocytes, potentially complicating their use in conjunction with active immunotherapy.
“They found that MK-2206, as well as the other Akt antagonist drugs, also had a tendency to suppress Th1 cytokine expression in stimulated human and murine lymphocytes, potentially complicating their use in conjunction with active immunotherapy”
After verifying that MK-2206 plus IFN-gamma could show similar combined effects against breast cancer lines, even in the absence of TNF-alpha, the authors tested in a rodent HER-2pos breast cancer model either a HER-2-based DC vaccine, or recombinant IFN-gamma with or without MK-2206 administration.
These findings suggest a combined therapy approach for Akt-targeting drugs that incorporates recombinant Interferon-gamma and is potentially translatable to humans.
Dr. Gary K. Koski from Kent State University said “Once existing only at the margins of cancer treatment, immunotherapy has now gained a strong claim as a distinct and accepted treatment modality, taking its place among the established approaches of surgery, radiation, cytotoxic agents and targeted drugs.”
Consistent with this notion, the authors and others have found that paired Th1 cytokines IFN-γ and TNF-α induced senescence and/or apoptosis in vitro for a variety of cancer cell lines.
Subsequent in vitro studies showed that ERpos BT-474 cells were relatively resistant to Th1 cytokines while ERneg SK-BR3 cells were more sensitive.
However, addition of anti-estrogen drugs to cytokines for BT-474 cells had about the same impact as cytokines alone on SKBR3, i. e. the drugs that blocked estrogen signaling appeared to sensitize estrogen-dependent cells to the Th1 cytokines.
Because Akt sits at the nexus of such important growth and survival signaling pathways, and because we previously showed that Th1 cytokines also trigger apoptosis while lowering expression of HER family oncodriver expression, the authors hypothesized that the combination of Th1 cytokines and Akt antagonists might make a particularly effective pairing useful for immunotherapy of breast cancer.
Since MK-2206 is one of the most potent and best-studied Akt agonists, they designed a series of studies around this agent to determine whether a phenotypically diverse panel of breast cancer lines would be susceptible to combined action of Th1 cytokines and MK-2206, whether this combination would enhance cell death through an apoptotic mechanism, and determine the effect of this treatment on the expression of important oncodrivers by breast cancer cells.
The Koski Research Team concluded in their Oncotarget Research Paper that few studies have examined the impact of Akt antagonist drugs on T cell function.
In contrast, the authors focused their investigation on suppression on T cell function, namely the capacity of antigen- and mitogen-stimulated cells to produce IFN-γ.
They showed that MK-2206, as well as all other tested Akt antagonists, strongly suppressed IFN-γ production by stimulated lymphocytes.
It is entirely possible that one of the reasons Akt inhibitor drugs have underperformed expectations clinically is that they simultaneously suppress activated T cells, and particularly their capacity to produce cytokines like IFN-γ which might be critical for anti-tumor activity by the immune system.
In light of this developing clinical trial, in the present study the authors placed particular emphasis on trastuzumab- and lapatinib-resistant cell lines, positioning Akt antagonist drugs as possible ways to deal with resistance to these more established drugs, should they come to be used more routinely in conjunction with IFN-γ.
References: Showalter L., Czerniecki B. J., Koski G. K. Th1 cytokines in conjunction with pharmacological Akt inhibition potentiate apoptosis of breast cancer cells in vitro and suppress tumor growth in vivo. Oncotarget. 2020; 11: 2873-2888. Retrieved from https://www.oncotarget.com/article/27556/text/
Elinor Greenberg, an internationally renowned Gestalt therapy trainer, think of schizoid personality disorder as the hidden disorder because most people with it are suffering very quietly. Unless they confide in you that they have this particular set of issues, you are unlikely to notice that anything is amiss. If you notice them at all, you are likely to assume that they are hardworking introverts who are not very interested in getting to know other people. However, their problems are much more serious than that.
In fact, so few people know about schizoid personality disorder that when she mention it, most people think she is referring to one of these much more serious and debilitating disorders: schizotypal disorder, schizophrenia, and schizoaffective disorder. However, schizophrenia and schizoaffective disorder are both serious psychoses and people with schizotypal disorder are more visibly odd and disturbed than people with schizoid personality disorder. The confusion comes from the prefix “schizo” which is a Latinized version of a Greek word meaning “split.” So to be clear, schizoid personality disorder is an entirely separate diagnosis from any of the ones above.
Note: In this article she will sometimes use SPD or schizoid as a shorthand way of saying that a particular person qualifies for a diagnosis of schizoid personality disorder. She may use the term adaptation instead of disorder in order to emphasize that this pattern, like all personality disorders, began as a small child’s creative adaptation to his or her family situation.
She suggested some problems which schizoid personality people do have..
Lack of Basic Trust: Early traumatic childhood experiences with uncaring, neglectful, intrusive, or abusive parents left my schizoid clients with the belief that relying on other people is inherently unsafe. Most report that by age 7 they had already realized that the adults around them could not be trusted to take care of them (Klein, 1995). Often, they had an abusive narcissistic or borderline parent who made their childhood a living hell.
Excessively Self-Sufficient: The schizoid solution to their lack of trust in other people is to try and become as independent and self-reliant as possible. Instead of looking to other people for help or validation, as her borderline and narcissistic clients do, they try to be entirely self-sufficient. They also tend to be very private and rarely share the details of their personal life with very many people. They exemplify the old saying: “She keeps herself to herself.” Most of her schizoid clients are good with money and are careful savers. They say that being financially independent gives them a greater sense of security.
Dissociation: When they were abused as children, her schizoid clients were unable to fight back or physically leave. However, they discovered how to dissociate from their body when they were frightened and go somewhere safe in their mind. Unfortunately, by the time they reach adulthood, the habit of dissociating when they feel stressed is so ingrained that they do it automatically—even when they would rather not. And, they cannot easily get out of that dissociated state. They describe that state as a sense of detachment from their body and their life, as if they were walking through a black and white movie about someone else. Nothing feels emotionally meaningful or real, but they can continue to function in a robotic way as long as necessary.
Social Fears: Most forms of interpersonal intimacy are experienced as potentially dangerous. This is especially true when the other person has a loud voice, domineering manner, and seems unpredictable.
Avoidant Behaviours: The basic response that most people with SPD have to their social fears is to physically and emotionally distance themselves as much as possible from other people. At a party, they tend to quietly stand at the edges of the group with a drink in their hand or they stay close to the nearest exist from the room.
Relationship Escape Hatches: They also tend to build escape hatches into their intimate relationships. By “escape hatch” she mean an easy way for them to justify periodically leaving the relationship, such as accepting a job that involves frequent travel or starting an affair with a married person who cannot be with them all of the time. The idea of having to be in a relationship with no barriers makes them very anxious. Her clients report feeling trapped and claustrophobic when they are expected to be in a close, ongoing relationship—even with someone they claim to love.
In and Out Relationships: One of the typically schizoid relationship patterns involves going in and out of the same romantic relationship repeatedly (Klein, 1995). Initially, they feel very much in love and try to get the other person to reciprocate their feelings. However, as soon as the other person returns their feelings and there are no longer any real barriers to intimacy, they become scared. They unconsciously shut down their feelings to protect themselves and find an excuse to back out of the relationship. However, as the time and distance between them and their ex increases, their fear diminishes. They start to feel love and attraction again. This leads them to approach their ex again and try to restart the relationship. Unless they get therapeutic help with their intimacy fears, they will just keep replaying this same pattern as long as the other person keeps taking them back.
Behavior May Appear Narcissistic: Sometimes, people in a romantic relationship with a schizoid person may mistake the above behaviours for narcissistic behavior because it appears superficially similar and feels so hurtful. However, the schizoid’s motive is quite different from the narcissist’s. Narcissists leave because they have become bored or angry, no longer idealize their partner, and want the validation of someone new. People with schizoid personality disorder leave because they feel trapped and afraid of being controlled (Greenberg, 2016).
Elaborate Fantasy Life: People who have made schizoid adaptations tend to substitute elaborate fantasy relationships for real relationships. Her schizoid clients explain that unlike in real life, in their fantasies they have total control over what happens. That makes fantasy relationships safer. Some people with SPD create such compelling and elaborate fantasy worlds that they go on to become famous writers.
Existential Fears: Her schizoid clients are the only ones who sometimes become preoccupied with the idea of death and the inherent meaninglessness of life. They may also express the fear that their distancing defenses will lead them becoming totally isolated from other human beings, in a void without connection to anybody, and they will not be able to reconnect.
Hides Emotional Reactions: This is in sharp contrast to people with borderline or narcissistic personality disorder who may loudly and publicly attack other people when they feel triggered. Most people with schizoid personality disorder quietly try to handle everything themselves. The last thing that they want is to involve anyone else in their problems.
Lacks Whole Object Relations and Object Constancy: In addition to the above adaptations that are specifically characteristic of SPD, people with SPD also lack whole object relations (WOR) and object constancy (OC), as do all people with personality disorders of any kind.
In brief, whole object relations is the capacity to see yourself and other people in a relatively, realistic, stable, and integrated way that simultaneously contains both like and disliked qualities. Object constancy is the ability to maintain whole object relations when you are angry, hurt, disappointed, or physically distant from the other person. Without WOR and OC, people are either seen as all-good or all-bad. The schizoid version of all-good or all-bad is “safe or unsafe.”
Summary: Schizoid personality disorder is believed to begin in early childhood as an adaptation to a major lack of attunement by the child’s caregivers. Instead of feeling safe, understood, and loved, the child experiences some combination of abuse, neglect, and intrusiveness. This leads the child to believe that other people cannot be trusted. As a result, in adulthood people with schizoid personality disorder work very hard to be as independent of other people as possible. Most people with schizoid adaptations end up living alone because they feel safer when they are by themselves. People with schizoid disorders mostly look like everyone else. They usually hold jobs, function well at work, and are not obviously disordered in any way—unless you know what to look for. They internalize their suffering and hide it from the rest of the world. When she asked one of her schizoid clients what she would like her to tell people about schizoid personality disorder, she said: “Tell them that they will never guess what we are really feeling from looking at us.”
References: (1) Klein, R. (1995). The self in exile: A developmental, self and object relations approach to the schizoid disorder of the self. In J. F Masterson & R. Klein (eds.), Disorders of the Self: New Therapeutic Horizons–The Masterson Approach. NY: Brunner/Mazel, p. 3-142. (2) Greenberg, E. (2016). Borderline, Narcissistic, and Schizoid Disorders: The Pursuit of Love, Admiration, and Safety. NY: Greenbrooke Press, Chapters 3 and 13.