Cognitive scientists attribute representations to complex systems in order to explain their behavior. The shocking facility with which Large Language Models (LLMs) perform difficult linguistic and non-linguistic tasks has generated an increasing amount of speculation concerning what sorts of internal representations might underlie this behavior (whether personal, sub-personal, and of which kinds) and what properties such representations might have (for instance, whether they are grounded). This paper aims to elaborate and defend a conservative explanatory methodology, based on analyses of particular LLM behaviors, according to which attribution of sub-personal representations is key to explaining model performance which is robust, systematic, and flexible, especially in zero-shot settings, and that behavioral benchmarking alone is insufficient to resolve questions about representation due to the mutual underdetermination of performance and competence. The resulting view should help frame future explanations of LLM behavior, and provide an empirically grounded alternative to mere a priori speculation.

Does tracking another agent's visual perspective depend on having a goal-albeit a remote one-to do so? In 5 experiments using indirect measures of visual perspective taking with a cartoon avatar, we examined whether and how adult perceivers' processing goals shape the incidental tracking of what objects the avatar sees (Level-1 perspective taking) and how the avatar sees those objects (Level-2 perspective taking). Process dissociation analyses, which aim to isolate calculation of the avatar's perspective as the process of focal interest, revealed that both Level-1 and Level-2 perspective calculation were consistently weaker when the avatar's perspective was less relevant for participants' own processing goals. This pattern of goal-dependent perspective tracking was also evident in behavioral analyses of interference from the avatar's differing perspective when reporting one's own perspective (i.e., altercentric interference). These results suggest that, although Level-1 and Level-2 visual perspective calculation may operate unintentionally, both also appear to depend on perceivers' processing goals. More generally, these findings advance understanding of processes underlying visual perspective taking and the conditional automaticity with which those processes operate. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Reasoning about other people's mental states has long been assumed to require active deliberation. Yet, evidence from indirect measures suggests that adults and children commonly display behavior indicative of having incidentally calculated both what other agents see (level-1 perspective taking) and how they see it (level-2 perspective taking). Here, we investigated the efficiency of such perspective calculation in adults. In four experiments using indirect measures of visual perspective taking, we imposed time pressure to constrain processing opportunity, and we used process-dissociation analyses to isolate perspective calculation as the process of focal interest. Results revealed that time pressure weakened level-2, but not level-1, perspective calculation-a pattern that was not evident in error-rate analyses. These findings suggest that perspective calculation may operate more efficiently in level-1 than in level-2 perspective taking. They also highlight the utility of the process-dissociation framework for unmasking processes that otherwise may go under-detected in behavior-level analyses.

The true impact and long-term damage to organs such as the lungs after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remain to be determined. Noninvasive molecularly targeted imaging may play a critical role in aiding visualization and understanding of the systemic damage. We have identified α_vβ₆ as a molecular target; an epithelium-specific cell surface receptor that is low or undetectable in healthy adult epithelium but upregulated in select injured tissues, including fibrotic lung. Herein we report the first human PET/CT images using the integrin α_vβ₆-binding peptide (¹⁸F-α_vβ₆-BP) in a patient 2 mo after the acute phase of infection. Minimal uptake of ¹⁸F-α_vβ₆-BP was noted in normal lung parenchyma, with uptake being elevated in areas corresponding to opacities on CT. This case suggests that ¹⁸F-α_vβ₆-BP PET/CT is a promising noninvasive approach to identify the presence and potentially monitor the persistence and progression of lung damage.

Empathy can be both beneficial and costly. This trade-off is pertinent for physicians who must care for patients while maintaining emotional distance to avoid burnout. Prior work using self-report and neurophysiological measures has found mixed evidence for differences in empathy between physicians and nonphysicians. We used implicit measurement and multinomial modeling to examine intentional empathy (IE) and unintentional empathy (UE) for pain among physicians and demographically matched nonphysicians. Relative to nonphysicians, physicians displayed greater ability to judge the painfulness of target experiences (i.e., IE). Contrary to some prior work, however, physicians and nonphysicians displayed comparable spontaneous resonance with distracter experiences (i.e., UE). These findings suggest that physicians may be more likely than nonphysicians to empathize with others’ pain when empathy aligns with their overt goals.

Cardiac ¹⁸F-FDG PET has been used in clinics to assess myocardial glucose metabolism. Its ability for imaging myocardial glucose transport, however, has rarely been exploited in clinics. Using the dynamic FDG-PET scans of ten patients with coronary artery disease, we investigate in this paper appropriate dynamic scan and kinetic modeling protocols for efficient quantification of myocardial glucose transport. Three kinetic models and the effect of scan duration were evaluated by using statistical fit quality, assessing the impact on kinetic quantification, and analyzing the practical identifiability. The results show that the kinetic model selection depends on the scan duration. The reversible two-tissue model was needed for a one-hour dynamic scan. The irreversible two-tissue model was optimal for a scan duration of around 10-15 minutes. If the scan duration was shortened to 2-3 minutes, a one-tissue model was the most appropriate. For global quantification of myocardial glucose transport, we demonstrated that an early dynamic scan with a duration of 10-15 minutes and irreversible kinetic modeling was comparable to the full one-hour scan with reversible kinetic modeling. Myocardial glucose transport quantification provides an additional physiological parameter on top of the existing assessment of glucose metabolism and has the potential to enable single tracer multiparametric imaging in the myocardium.

Objective

To compare the relative efficacy of current and investigational biologic and oral small molecule (OSM) treatments for active ankylosing spondylitis (AS).

Methods

A systematic literature review was conducted to identify all phase 2/3 randomized trials of interest in patients with AS. Outcomes assessed were ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) and C-reactive protein (CRP) at weeks 12-16. Bayesian network meta-analyses were conducted for outcomes using a random effects model. Baseline-risk adjustment was also conducted to account for differences in placebo response across studies. Surface Under the Cumulative Ranking curve (SUCRA) values are reported, reflecting the relative probability that intervention was the best of all interventions.

Results

The investigational agent tofacitinib 5 mg was the top-ranked treatment (SUCRA, 93%) for ASAS20 response, followed by intravenous (IV) golimumab 2 mg/kg (90%). Golimumab IV 2 mg/kg and infliximab 5 mg/kg were the top two ranked treatments for change from baseline in BASFI (golimumab IV, 81%; infliximab, 80%) and change from baseline in CRP (infliximab, 90%; golimumab IV, 82%).

Conclusions

Two approved therapies (golimumab IV, infliximab) and one investigational product ranked highest for efficacy in AS. Key Points • Although golimumab IV, infliximab, and tofacitinib ranked highest for efficacy in AS, differences in efficacy between approved and investigational therapies were not statistically significant.

Purpose

The study was undertaken to develop and evaluate the potential of an integrin α_vβ₆-binding peptide (α_vβ₆-BP) for noninvasive imaging of a diverse range of malignancies with PET.

Experimental design

The peptide α_vβ₆-BP was prepared on solid phase and radiolabeled with 4-[¹⁸F]fluorobenzoic acid. In vitro testing included ELISA, serum stability, and cell binding studies using paired α_vβ₆-expressing and α_vβ₆-null cell lines. In vivo evaluation (PET/CT, biodistribution, and autoradiography) was performed in a mouse model bearing the same paired α_vβ₆-expressing and α_vβ₆-null cell xenografts. A first-in-human PET/CT imaging study was performed in patients with metastatic lung, colon, breast, or pancreatic cancer.

Results

[¹⁸F]α_vβ₆-BP displayed excellent affinity and selectivity for the integrin α_vβ₆ in vitro [IC₅₀(α_vβ₆) = 1.2 nmol/L vs IC₅₀(α_vβ₃) >10 μmol/L] in addition to rapid target-specific cell binding and internalization (72.5% ± 0.9% binding and 52.5% ± 1.8%, respectively). Favorable tumor affinity and selectivity were retained in the mouse model and excretion of unbound [¹⁸F]α_vβ₆-BP was rapid, primarily via the kidneys. In patients, [¹⁸F]α_vβ₆-BP was well tolerated without noticeable adverse side effects. PET images showed significant uptake of [¹⁸F]α_vβ₆-BP in both the primary lesion and metastases, including metastasis to brain, bone, liver, and lung.

Conclusions

The clinical impact of [¹⁸F]α_vβ₆-BP PET imaging demonstrated in this first-in-human study is immediate for a broad spectrum of malignancies.