Dosage appears to play a crucial role, as the meta-analysis indicated that histological remission rates were significantly higher with the use of double doses of PPIs compared to standard doses (51.7% vs. 28.3%, p < 0.005). The duration of treatment also seems to be important, with the EoE CONNECT database study suggesting that prolonging the initial treatment period from 8 to 12 weeks may increase the likelihood of achieving remission.
The traditional understanding of how PPIs might benefit patients with EoE has primarily focused on their ability to suppress gastric acid production. Gastroesophageal reflux, including acid reflux, can contribute to esophageal inflammation and potentially exacerbate EoE. By reducing gastric acid secretion, PPIs may alleviate this contributing factor, thereby reducing esophageal inflammation. Acid-peptic damage to the esophageal epithelium can increase its permeability, potentially allowing for greater penetration of allergens that trigger the immune response in EoE. Furthermore, acid exposure can enhance the expression of inflammatory mediators and adhesion molecules, potentially leading to the recruitment of eosinophils. Thus, the acid-suppressing effects of PPIs could indirectly benefit EoE by mitigating these processes.
However, accumulating evidence suggests that PPIs may also exert direct anti-inflammatory effects on the esophageal mucosa, independent of their acid-suppressing properties. In vitro studies have demonstrated that PPIs, such as omeprazole and lansoprazole, can inhibit the Th2 cytokine-stimulated secretion of eotaxin-3, a key chemokine responsible for the recruitment of eosinophils to the esophagus.
Progression of PPI therapy from diagnostic tool to therapy for EoE. Initial belief that EoE was a consequence of GERD led to early interest in PPIs as a therapy for EoE. Next, it was hypothesized that PPI-responsive esophageal eosinophilia (PPI-REE) was a condition distinct from EoE. A lack of response to PPIs was subsequently viewed as an essential diagnostic criterion for EoE. Subsequently, characterizations of PPI-REE and EoE patients at the molecular level showed that the two conditions are virtually identical leading to the hypothesis that they are at different points along a continuum. Recent guidelines, enlightened by this observation, now view PPIs as a therapy rather than a diagnostic for EoE.
We’re betting that the lion’s share of value from AI will come from automating ordinary labor tasks rather than from “geniuses in a data center”. Currently, AI models have serious shortcomings that render most of this enormous value out of reach. They are unreliable, lack robust long-context capabilities, struggle with agency and multimodality, and can’t execute long-term plans without going off the rails. To overcome these limitations, Mechanize will produce the data and evals necessary for comprehensively automating work. Our digital environments will act as practical simulations of real-world work scenarios, enabling agents to learn useful abilities through RL. The market potential here is absurdly large: workers in the US are paid around $18 trillion per year in aggregate. For the entire world, the number is over three times greater, around $60 trillion per year.
1h 49mApril 14, 2025 Import AI 408: Multi-code SWE Bench; backdoored Unitree robots; and what AI 2027 is telling us by Jack Clark Welcome to Import AI, a newsletter about AI research. Import AI runs on lattes, ramen, and feedback from readers. If you’d like to support this, please subscribe. Subscribe now German researchers find undocumented backdoor in Unitree robots: …Exactly the kind of thing a superintelligence would want to exploit during a hard takeoff… German security firm ‘Think Awesome’ has analyzed the Unitree Go1 quadruped robot dog and found an undocumented backdoor which lets people tunnel into any of these dogs and view their camera feeds. “Unitree did pre-install a tunnel without notifying its customers.
We're currently living through the fastest-growing time in history. This rate of growth hasn't gone on long, and can't go on indefinitely (there aren't enough atoms in the galaxy to sustain this rate of growth for even another 10,000 years). And if we get further acceleration in this rate of growth - in line with historical acceleration - we could reach the limits of what's possible more quickly: within this century
And yet at the same time I do see a totally invisible mental image of a table in that same empty space, or at least in a space that is somehow superimposed on my normal visual space. I can both see the mental image, in an invisible ghostly way, and at the same time I don’t see anything at all. Furthermore, what little I see of the imagined table does not always have a specific location, nor a specific size or scale, nor a specific viewing angle, nor a specific color or furniture style. The “image” of the table (if it can be called such) often appears either fleeting and unstable in location, scale, and orientation, or it appears totally abstract, non-spatial, as if expressed only in some symbolic non-spatial code, like a node in a neural network model that is labeled “table”. It is this fleeting evanescence and instability of the mental image that allows so many to deny its very existence as a spatially extended image in our imagination.
The fact that it is possible to form a mental image with a specific location and specific dimensions, and to mime its morphology with your palms, is proof that mental images can exist as stable three-dimensional structures, and that they can carry a specific information content. And the mental image can be formulated to have a specific location and spatial extent, even if it is not usually specified so precisely, but often remains in an indeterminate state. The fleeting evanescence and instability of many mental images should not be viewed as counter-evidence for their existence as images, but is merely evidence of a fleeting and unstable imaging system, one that is capable of representing multiple possibilities all superimposed, much like a quantum particle that can exist in multiple states simultaneously. Like a quantum particle, the mechanism or principle underlying the mental image can apparently flip or morph continuously into different forms, unless it is held to a stable state by an act of will.
has called this kind of vision “amodal” perception, because it is perception in the absence of a particular visual modality, such as color or brightness. We see a square in our imagination, but it is in a kind of invisible outline form, like a figure in a geometry text, without color or substance, just a shape.
One reason why this amodal percept is so easily overlooked, is that it is not really a visual experience as such, even though it is often informed by a visual stimulus. When I encounter a box in pitch darkness, or with eyes closed, and feel it with my palms, I get the same amodal experience of a rectangular volume in a specific location in my space, and I perceive the whole box, through to its rear surfaces, even though I palm only selected faces or corners of the box at a time. And when I turn on the lights, or open my eyes, the tactile texture of the box felt by my palms is experienced on the very same rectangular volume as are its color and brightness that I perceive visually.
In other words, the spatial structure that is our amodal experience of the world is the common ground, or lingua franca, that unites all sensory experience in a modality-independent structural representation of the world, and that amodal structure represents our perceptual and cognitive understanding of the world.
Amodal perception is the earliest, most basic form of mental imagery, one that we certainly share with almost all visual creatures. But amodal perception is also the door that opened perception to cognition and free-wheeling mental imagery, and true human intelligence, connecting the world of direct experience to the world of imagination.