Limited information-processing capacity in vision explains number psychophysics.

Humans and other animals are able to perceive and represent a number of objects present in a scene, a core cognitive ability thought to underlie the development of mathematics. However, the perceptual mechanisms that underpin this capacity remain poorly understood. Here, we show that our visual sense of number derives from a visual system designed to efficiently encode the location of objects in scenes. Using a mathematical model, we demonstrate that an efficient but information-limited encoding of objects' locations can explain many key aspects of number psychophysics, including subitizing, Weber's law, underestimation, and effects of exposure time. In two experiments (N = 100 each), we find that this model of visual encoding captures human performance in both a change-localization task and a number estimation task. In a third experiment (N = 100), we find that individual differences in change-localization performance are highly predictive of differences in number estimation, both in terms of overall performance and inferred model parameters, with participants having numerically indistinguishable inferred information capacities across tasks. Our results therefore indicate that key psychophysical features of numerical cognition do not arise from separate modules or capacities specific to number, but rather as by-products of lower level constraints on perception. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Response to Difficulty Drives Variation in IQ Test Performance.

In a large (N = 300), pre-registered experiment and data analysis model, we find that individual variation in overall performance on Raven's Progressive Matrices is substantially driven by differential strategizing in the face of difficulty. Some participants choose to spend more time on hard problems while others choose to spend less and these differences explain about 42% of the variance in overall performance. In a data analysis jointly predicting participants' reaction times and accuracy on each item, we find that the Raven's task captures at most half of participants' variation in time-controlled ability (48%) down to almost none (3%), depending on which notion of ability is assumed. Our results highlight the role that confounding factors such as motivation play in explaining individuals' differential performance in IQ testing.

The algorithmic origins of counting.

The study of how children learn numbers has yielded one of the most productive research programs in cognitive development, spanning empirical and computational methods, as well as nativist and empiricist philosophies. This paper provides a tutorial on how to think computationally about learning models in a domain like number, where learners take finite data and go far beyond what they directly observe or perceive. To illustrate, this paper then outlines a model which acquires a counting procedure using observations of sets and words, extending the proposal of Piantadosi et al. (2012). This new version of the model responds to several critiques of the original work and outlines an approach which is likely appropriate for acquiring further aspects of mathematics.

The Influence of Social Determinants on Receiving Outpatient Treatment with Monoclonal Antibodies, Disease Risk, and Effectiveness for COVID-19.

BACKGROUND: Limited research has studied the influence of social determinants of health (SDoH) on the receipt, disease risk, and subsequent effectiveness of neutralizing monoclonal antibodies (nMAbs) for outpatient treatment of COVID-19. OBJECTIVE: To examine the influence of SDoH variables on receiving nMAb treatments and the risk of a poor COVID-19 outcome, as well as nMAb treatment effectiveness across SDoH subgroups. DESIGN: Retrospective observational study utilizing electronic health record data from four health systems. SDoH variables analyzed included race, ethnicity, insurance, marital status, Area Deprivation Index, and population density. PARTICIPANTS: COVID-19 patients who met at least one emergency use authorization criterion for nMAb treatment. MAIN MEASURE: We used binary logistic regression to examine the influence of SDoH variables on receiving nMAb treatments and risk of a poor outcome from COVID-19 and marginal structural models to study treatment effectiveness. RESULTS: The study population included 25,241 (15.1%) nMAb-treated and 141,942 (84.9%) non-treated patients. Black or African American patients were less likely to receive treatment than white non-Hispanic patients (adjusted odds ratio (OR) = 0.86; 95% CI = 0.82-0.91). Patients who were on Medicaid, divorced or widowed, living in rural areas, or living in areas with the highest Area Deprivation Index (most vulnerable) had lower odds of receiving nMAb treatment, but a higher risk of a poor outcome. For example, compared to patients on private insurance, Medicaid patients had 0.89 (95% CI = 0.84-0.93) times the odds of receiving nMAb treatment, but 1.18 (95% CI = 1.13-1.24) times the odds of a poor COVID-19 outcome. Age, comorbidities, and COVID-19 vaccination status had a stronger influence on risk of a poor outcome than SDoH variables. nMAb treatment benefited all SDoH subgroups with lower rates of 14-day hospitalization and 30-day mortality. CONCLUSION: Disparities existed in receiving nMAbs within SDoH subgroups despite the benefit of treatment across subgroups.

Diverse mathematical knowledge among indigenous Amazonians.

We investigate number and arithmetic learning among a Bolivian indigenous people, the Tsimane', for whom formal schooling is comparatively recent in history and variable in both extent and consistency. We first present a large-scale meta-analysis on child number development involving over 800 Tsimane' children. The results emphasize the impact of formal schooling: Children are only found to be full counters when they have attended school, suggesting the importance of cultural support for early mathematics. We then test especially remote Tsimane' communities and document the development of specialized arithmetical knowledge in the absence of direct formal education. Specifically, we describe individuals who succeed on arithmetic problems involving the number five-which has a distinct role in the local economy-even though they do not succeed on some lower numbers. Some of these participants can perform multiplication with fives at greater accuracy than addition by one. These results highlight the importance of cultural factors in early mathematics and suggest that psychological theories of number where quantities are derived from lower numbers via repeated addition (e.g., a successor function) are unlikely to explain the diversity of human mathematical ability.

The Plausibility of Sampling as an Algorithmic Theory of Sentence Processing.

Words that are more surprising given context take longer to process. However, no incremental parsing algorithm has been shown to directly predict this phenomenon. In this work, we focus on a class of algorithms whose runtime does naturally scale in surprisal-those that involve repeatedly sampling from the prior. Our first contribution is to show that simple examples of such algorithms predict runtime to increase superlinearly with surprisal, and also predict variance in runtime to increase. These two predictions stand in contrast with literature on surprisal theory (Hale, 2001; Levy, 2008a) which assumes that the expected processing cost increases linearly with surprisal, and makes no prediction about variance. In the second part of this paper, we conduct an empirical study of the relationship between surprisal and reading time, using a collection of modern language models to estimate surprisal. We find that with better language models, reading time increases superlinearly in surprisal, and also that variance increases. These results are consistent with the predictions of sampling-based algorithms.

Latent Diversity in Human Concepts.

Many social and legal conflicts hinge on semantic disagreements. Understanding the origins and implications of these disagreements necessitates novel methods for identifying and quantifying variation in semantic cognition between individuals. We collected conceptual similarity ratings and feature judgements from a variety of words in two domains. We analyzed this data using a non-parametric clustering scheme, as well as an ecological statistical estimator, in order to infer the number of different variants of common concepts that exist in the population. Our results show at least ten to thirty quantifiably different variants of word meanings exist for even common nouns. Further, people are unaware of this variation, and exhibit a strong bias to erroneously believe that other people share their semantics. This highlights conceptual factors that likely interfere with productive political and social discourse.

Dendritic cell vaccine trials in gliomas: Untangling the lines.

Glioblastoma is a deadly brain tumor without any significantly successful treatments to date. Tumor antigen-targeted immunotherapy platforms including peptide and dendritic cell (DC) vaccines, have extended survival in hematologic malignancies. The relatively "cold" tumor immune microenvironment and heterogenous nature of glioblastoma have proven to be major limitations to translational application and efficacy of DC vaccines. Furthermore, many DC vaccine trials in glioblastoma are difficult to interpret due to a lack of contemporaneous controls, absence of any control comparison, or inconsistent patient populations. Here we review glioblastoma immunobiology aspects that are relevant to DC vaccines, review the clinical experience with DC vaccines targeting glioblastoma, discuss challenges in clinical trial design, and summarize conclusions and directions for future research for the development of effective DC vaccines for patients.

Immunogenicity of quadrivalent meningococcal conjugate vaccine in frequent platelet donors.

Frequent plateletpheresis is associated with severe lymphopenia of uncertain clinical significance. We assessed the functional impact of frequent platelet donations and associated lymphopenia on the response to neoantigens. We conducted a prospective study of 102 platelet donors (HIV uninfected) who were naive to meningococcal vaccination recruited at Brigham and Women's Hospital. One dose of quadrivalent meningococcal conjugate vaccine was administered. Seroresponse was defined as a fourfold increase of serum bactericidal antibody titers and seroprotection was defined as postvaccination titers of ≥1:8, for each of the 4 vaccine antigens (A, C, W, and Y). Mean age of participants was 61 years, 69% were male, and medial number of platelet donations in prior year was 14 (interquartile range, 4-20). Frequent platelet donors had a low CD4 count (14% with ≤200/µL and 34% with ≤350/µL). Seroresponse rates varied from 68% for serogroup Y to 86% for serogroup A and were higher for participants with baseline titers of <1:8. Postvaccination seroprotection rates varied from 76% for serogroup Y to 96% for serogroup A. After adjustments for age, sex, and frequent donations, lower total lymphocyte or lower CD4 counts were not associated with lower responses. These data suggest no impairment by plateletpheresis-associated lymphopenia on response to these neoantigens. This trial was registered at www.clinicaltrials.gov as #NCT04224311.

Real-time inference in communication across cultures: Evidence from a nonindustrialized society.

In everyday communication, speakers and listeners make sophisticated inferences about their conversation partner's intended meaning. They combine their knowledge of the visuospatial context with reasoning about the other person's knowledge state and rely on shared assumptions about how language is used to express communicative intentions. However, these assumptions may differ between languages of nonindustrialized-where conversations often primarily take place within a, so-called, society of intimates-and industrialized cultures-societies of strangers. Here, we study inference in communication in the Tsimane', an indigenous people of the Bolivian Amazon, who have little contact with industrialization or formal education. Using a referential communication task, we probe how Tsimane' speakers refer to objects in the world around them when there are potential ambiguities (e.g., referring to a cup when there are multiple cups in view) across different visual contexts. Using an eye-tracking task, we probe the real-time inferences that Tsimane' listeners make about the speaker's intentions. We find that Tsimane' speakers use visual (color, size) contrasts to disambiguate referents (e.g., "Hand me the small cup"), much like English speakers, and they predictively direct their gaze to objects in a contrast set when they hear a modifier (e.g., "small"). Despite myriad cultural and linguistic dissimilarities between the two populations, the qualitative patterns of behavior and eye-gaze of Tsimane' and English speakers were strikingly similar, suggesting that the communicative expectations underlying many everyday inferences may be shared across cultures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Neutralizing Monoclonal Antibody Use and COVID-19 Infection Outcomes.

Importance: Evidence on the effectiveness and safety of COVID-19 therapies across a diverse population with varied risk factors is needed to inform clinical practice. Objective: To assess the safety of neutralizing monoclonal antibodies (nMAbs) for the treatment of COVID-19 and their association with adverse outcomes. Design, Setting, and Participants: This retrospective cohort study included 167 183 patients from a consortium of 4 health care systems based in California, Minnesota, Texas, and Utah. The study included nonhospitalized patients 12 years and older with a positive COVID-19 laboratory test collected between November 9, 2020, and January 31, 2022, who met at least 1 emergency use authorization criterion for risk of a poor outcome. Exposure: Four nMAb products (bamlanivimab, bamlanivimab-etesevimab, casirivimab-imdevimab, and sotrovimab) administered in the outpatient setting. Main Outcomes and Measures: Clinical and SARS-CoV-2 genomic sequence data and propensity-adjusted marginal structural models were used to assess the association between treatment with nMAbs and 4 outcomes: all-cause emergency department (ED) visits, hospitalization, death, and a composite of hospitalization or death within 14 days and 30 days of the index date (defined as the date of the first positive COVID-19 test or the date of referral). Patient index dates were categorized into 4 variant epochs: pre-Delta (November 9, 2020, to June 30, 2021), Delta (July 1 to November 30, 2021), Delta and Omicron BA.1 (December 1 to 31, 2021), and Omicron BA.1 (January 1 to 31, 2022). Results: Among 167 183 patients, the mean (SD) age was 47.0 (18.5) years; 95 669 patients (57.2%) were female at birth, 139 379 (83.4%) were White, and 138 900 (83.1%) were non-Hispanic. A total of 25 241 patients received treatment with nMAbs. Treatment with nMAbs was associated with lower odds of ED visits within 14 days (odds ratio [OR], 0.76; 95% CI, 0.68-0.85), hospitalization within 14 days (OR, 0.52; 95% CI, 0.45-0.59), and death within 30 days (OR, 0.14; 95% CI, 0.10-0.20). The association between nMAbs and reduced risk of hospitalization was stronger in unvaccinated patients (14-day hospitalization: OR, 0.51; 95% CI, 0.44-0.59), and the associations with hospitalization and death were stronger in immunocompromised patients (hospitalization within 14 days: OR, 0.31 [95% CI, 0.24-0.41]; death within 30 days: OR, 0.13 [95% CI, 0.06-0.27]). The strength of associations of nMAbs increased incrementally among patients with a greater probability of poor outcomes; for example, the ORs for hospitalization within 14 days were 0.58 (95% CI, 0.48-0.72) among those in the third (moderate) risk stratum and 0.41 (95% CI, 0.32-0.53) among those in the fifth (highest) risk stratum. The association of nMAb treatment with reduced risk of hospitalizations within 14 days was strongest during the Delta variant epoch (OR, 0.37; 95% CI, 0.31-0.43) but not during the Omicron BA.1 epoch (OR, 1.29; 95% CI, 0.68-2.47). These findings were corroborated in the subset of patients with viral genomic data. Treatment with nMAbs was associated with a significant mortality benefit in all variant epochs (pre-Delta: OR, 0.16 [95% CI, 0.08-0.33]; Delta: OR, 0.14 [95% CI, 0.09-0.22]; Delta and Omicron BA.1: OR, 0.10 [95% CI, 0.03-0.35]; and Omicron BA.1: OR, 0.13 [95% CI, 0.02-0.93]). Potential adverse drug events were identified in 38 treated patients (0.2%). Conclusions and Relevance: In this study, nMAb treatment for COVID-19 was safe and associated with reductions in ED visits, hospitalization, and death, although it was not associated with reduced risk of hospitalization during the Omicron BA.1 epoch. These findings suggest that targeted risk stratification strategies may help optimize future nMAb treatment decisions.

Cognitive Mechanisms Underlying Recursive Pattern Processing in Human Adults.

The capacity to generate recursive sequences is a marker of rich, algorithmic cognition, and perhaps unique to humans. Yet, the precise processes driving recursive sequence generation remain mysterious. We investigated three potential cognitive mechanisms underlying recursive pattern processing: hierarchical reasoning, ordinal reasoning, and associative chaining. We developed a Bayesian mixture model to quantify the extent to which these three cognitive mechanisms contribute to adult humans' performance in a sequence generation task. We further tested whether recursive rule discovery depends upon relational information, either perceptual or semantic. We found that the presence of relational information facilitates hierarchical reasoning and drives the generation of recursive sequences across novel depths of center embedding. In the absence of relational information, the use of ordinal reasoning predominates. Our results suggest that hierarchical reasoning is an important cognitive mechanism underlying recursive pattern processing and can be deployed across embedding depths and relational domains.

Current drug development and trial designs in neuro-oncology: report from the first American Society of Clinical Oncology and Society for Neuro-Oncology Clinical Trials Conference.

Successful drug development for people with cancers of the CNS has been challenging. There are multiple barriers to successful drug development including biological factors, rarity of the disease, and ineffective use of clinical trials. Based upon a series of presentations at the First Central Nervous System Clinical Trials Conference hosted by the American Society of Clinical Oncology and the Society for Neuro-Oncology, we provide an overview on drug development and novel trial designs in neuro-oncology. This Review discusses the challenges of therapeutic development in neuro-oncology and proposes strategies to improve the drug discovery process by enriching the pipeline of promising therapies, optimising trial design, incorporating biomarkers, using external data, and maximising efficacy and reproducibility of clinical trials.

Origins of Hierarchical Logical Reasoning.

Hierarchical cognitive mechanisms underlie sophisticated behaviors, including language, music, mathematics, tool-use, and theory of mind. The origins of hierarchical logical reasoning have long been, and continue to be, an important puzzle for cognitive science. Prior approaches to hierarchical logical reasoning have often failed to distinguish between observable hierarchical behavior and unobservable hierarchical cognitive mechanisms. Furthermore, past research has been largely methodologically restricted to passive recognition tasks as compared to active generation tasks that are stronger tests of hierarchical rules. We argue that it is necessary to implement learning studies in humans, non-human species, and machines that are analyzed with formal models comparing the contribution of different cognitive mechanisms implicated in the generation of hierarchical behavior. These studies are critical to advance theories in the domains of recursion, rule-learning, symbolic reasoning, and the potentially uniquely human cognitive origins of hierarchical logical reasoning.

Stochastic Time-Series Analyses Highlight the Day-To-Day Dynamics of Lexical Frequencies.

Standard models in quantitative linguistics assume that word usage follows a fixed frequency distribution, often Zipf's law or a close relative. This view, however, does not capture the near daily variations in topics of conversation, nor the short-term dynamics of language change. In order to understand the dynamics of human language use, we present a corpus of daily word frequency variation scraped from online news sources every 20 min for more than 2 years. We construct a simple time-varying model with a latent state, which is observed via word frequency counts. We use Bayesian techniques to infer the parameters of this model for 20,000 words, allowing us to convert complex word-frequency trajectories into low-dimensional parameters in word usage. By analyzing the inferred parameters of this model, we quantify the relative mobility and drift of words on a day-to-day basis, while accounting for sampling error. We quantify this variation and show evidence against "rich-get-richer" models of word use, which have been previously hypothesized to explain statistical patterns in language.

Different reference frames on different axes: Space and language in indigenous Amazonians.

Spatial cognition is central to human behavior, but the way people conceptualize space varies within and across groups for unknown reasons. Here, we found that adults from an indigenous Bolivian group used systematically different spatial reference frames on different axes, according to known differences in their discriminability: In both verbal and nonverbal tests, participants preferred allocentric (i.e., environment-based) space on the left-right axis, where spatial discriminations (like "b" versus "d") are notoriously difficult, but the same participants preferred egocentric (i.e., body-based) space on the front-back axis, where spatial discrimination is relatively easy. The results (i) establish a relationship between spontaneous spatial language and memory across axes within a single culture, (ii) challenge the claim that each language group has a predominant spatial reference frame at a given scale, and (iii) suggest that spatial thinking and language may both be shaped by spatial discrimination abilities, as they vary across cultures and contexts.

Update on the clinical trial landscape: analysis of ClinicalTrials.gov registration data, 2000-2020.

BACKGROUND: The clinical trial landscape has evolved over the last two decades, shaped by advances in therapeutics and drug development and innovation in trial design and methods. The tracking of such changes became possible with trial registration, providing the public with a window into the massive clinical research enterprise. The ClinicalTrials.gov website was launched in 2000 by the NIH National Library of Medicine and is the largest clinical trial registry worldwide. The purpose of this analysis is to describe the composition and methodologic features of clinical trials as registered on ClinicalTrials.gov and to identify trends over time. METHODS: We analyzed data from the publicly available Clinical Trials Transformation Initiative Aggregate Analysis of ClinicalTrials.gov (AACT) database, focusing on trials (interventional studies) started between 1 January 2000 through 31 December 2020. Characteristics of design (e.g., phase, randomization, use of masking, number of treatment groups, sample size), eligibility criteria (age groups, gender), interventions, conditions, and funders (primary sponsor) were tabulated over time, by year trial started. RESULTS: There were 274,043 registered interventional studies (trials) included in the analysis. Most trials were reported as randomized (65%); single site (60%); parallel-group (56%); funded by other sources (e.g., individuals, universities, and community-based organizations) (65%); and involving drug interventions (55%). Notable trends include an increase in the proportion of registered trials without FDA-defined phases ("Phase N/A") over time, a decrease in proportion of trials that involve drugs or report treatment as a primary purpose, declining sample size and time to complete trials, and an increase in proportion of trials reporting results among completed trials. The proportion of missing registration fields has also decreased over time and more trials make protocols and other documents available. There is a current need to expand the registration fields in ClinicalTrials.gov to adapt to the evolving trial designs and reduce the number of trials categorized as "other." Observed trends may be explained by changes in trial regulations as well as expanding and evolving trial designs, interventions, and outcome types. CONCLUSIONS: Clinical trial registration has transformed how trial information is accessed, disseminated, and used. As clinical trials evolve and regulations change, trial registries, including ClinicalTrials.gov, will continue to provide a means to access and follow trials over time, thus informing future trial design and highlighting the value of this tremendous resource.

Verbal counting and the timing of number acquisition in an indigenous Amazonian group.

Children in industrialized cultures typically succeed on Give-N, a test of counting ability, by age 4. On the other hand, counting appears to be learned much later in the Tsimane', an indigenous group in the Bolivian Amazon. This study tests three hypotheses for what may cause this difference in timing: (a) Tsimane' children may be shy in providing behavioral responses to number tasks, (b) Tsimane' children may not memorize the verbal list of number words early in acquisition, and/or (c) home environments may not support mathematical learning in the same way as in US samples, leading Tsimane' children to primarily acquire mathematics through formalized schooling. Our results suggest that most of our subjects are not inhibited by shyness in responding to experimental tasks. We also find that Tsimane' children (N = 100, ages 4-11) learn the verbal list later than US children, but even upon acquiring this list, still take time to pass Give-N tasks. We find that performance in counting varies across tasks and is related to formal schooling. These results highlight the importance of formal education, including instruction in the count list, in learning the meanings of the number words.