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In the study of perceptual categorization, a key distinction is made between separable and integral dimensions. Separable dimensions are easy to attend in isolation, while integral dimensions are not. Little et al. (2016) showed that when trial-by-trial responses are analyzed, a consistent pattern of sequential effects was found in a modified Garner paradigm using integral-dimension stimuli. The present experiments investigated whether these pronounced sequential effects are also found with separable-dimension stimuli. Four experiments using two different types of separable dimensions were conducted. The results indicated that similar patterns of sequential effects were present for separable-dimension stimuli, but, unlike for integral dimensions, the effect of a change in the irrelevant dimension in the filtering task was not found. Further, for separable dimensions, the overall pattern of sequential effects did not vary between the Garner tasks (i.e., control, correlated, and filtering). To explain these results, we fit a sequence-sensitive exemplar model and compared the fits of this model to a novel sequence-sensitive feature model, in which only the relevant feature influences the categorization decision. We found that the full exemplar model provided a more compelling account of both our separable dimension data and the integral dimension data of Little et al. (2016). These findings provide a more complete understanding of perceptual categorization and add to the growing body of literature on the prevalence and critical implications of strong sequential effects in cognitive tasks. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The purpose of this study was to investigate the psychometric properties of the remote first aid self-efficacy scale (RFA SES). The RFA SES is a 30-item self-report scale developed in response to emerging evidence showing that self-efficacy is predictive of performance.Trained alumni from Wilderness Medical Associates (WMA) training courses and less trained students from Laurentian University (LU) were recruited via email to complete an online questionnaire at 2 different periods (T1 and T2). The questionnaire included demographic questions, the 30-item RFA SES, the 10-item Connor-Davidson resilience scale (CD-RISC), and the 10-item generalized self-efficacy scale (GSES). Data analysis included assessment of the dimensionality, reliability, and validity of the scale.There were 448 alumni from WMA and 1106 students from LU who participated in the study. The RFA SES demonstrated a clear unidimensional structure. The mean interitem correlation was 0.75 at T1. Test-retest reliability (T1 to T2) was high for both the LU group (intraclass correlation [ICC]=0.90) and the WMA group (ICC=0.92). Moderate correlations were found between RFA SES and CD-RISC (r=0.42, P0.001), a general measure of resilience, and the GSES (r=0.48, P0.001), a general measure of self-efficacy. Wilderness Medical Associates participants showed higher mean scores than LU students at T1 (t [569]=16.2, P0.001).The RFA SES is a unidimensional, reliable, and potentially valid scale. Further research should focus on item reduction followed by additional tests of reliability and validity.

Conventional drug delivery systems have been applied to a myriad of active ingredients but may be difficult to tailor for a given drug. Herein, we put forth a new strategy, which designs and selects the drug delivery material by considering the properties of encapsulated drugs (even multiple drugs, simultaneously). Specifically, through an in-silico screening process of 5109 MOFs using grand canonical Monte Carlo simulations, a customized MOF (referred as BIO-MOF-100) was selected and experimentally verified to be biologically stable, and capable of loading 3 anti-Tuberculosis drugs Rifampicin+Isoniazid+Pyrazinamide at 10% + 28% + 23% wt/wt (total 50% by weight). Notably, the customized BIO-MOF-100 delivery system cleared naturally Pyrazinamide-resistant Bacillus Calmette-Guérin, reduced growth of virulent Erdman infection in macaque macrophages 10-100-fold compared to soluble drugs in vitro and was also significantly reduced Erdman growth in mice. These data suggest that the methodology of identifying-synthesizing materials can be used to generate solutions for challenging applications such as simultaneous delivery of multiple, small hydrophilic and hydrophobic molecules in the same molecular framework.

Impaired beta-cell function is a recognized cornerstone of diabetes pathophysiology. Estimates of insulin secretory capacity are useful to inform clinical practice, helping to classify types of diabetes, complication risk stratification and to guide treatment decisions. Because C-peptide secretion mirrors beta-cell function, it has emerged as a valuable clinical biomarker, mainly in autoimmune diabetes and especially in adult-onset diabetes. Nonetheless, the lack of robust evidence about the clinical utility of C-peptide measurement in type 2 diabetes, where insulin resistance is a major confounder, limits its use in such cases. Furthermore, problems remain in the standardization of the assay for C-peptide, raising concerns about comparability of measurements between different laboratories. To approach the heterogeneity and complexity of diabetes, reliable, simple and inexpensive clinical markers are required that can inform clinicians about probable pathophysiology and disease progression, and so enable personalization of management and therapy. This review summarizes the current evidence base about the potential value of C-peptide in the management of the two most prevalent forms of diabetes (type 2 diabetes and autoimmune diabetes) to address how its measurement may assist daily clinical practice and to highlight current limitations and areas of uncertainties to be covered by future research.

Particles synthesized from biodegradable polymers hold great potential as controlled drug delivery systems. Continuous flow platforms based on microfluidics offer attractive advantages over conventional batch-emulsification techniques for the scalable fabrication of drug-loaded particles with controlled physicochemical properties. However, widespread utilization of microfluidic technologies for the manufacturing of drug-loaded particles has been hindered largely by the lack of practical guidelines toward cost-effective development and reliable operation of microfluidic systems. Here, we present a framework for rational design and construction of microfluidic systems using commercially available components for high-throughput production of uniform biodegradable particles encapsulating drugs. We also demonstrate successful implementation of this framework to devise a robust microfluidic system that is capable of producing drug-carrying particles with desired characteristics. The guidelines provided in this study will likely help broaden the applicability of microfluidic technologies for the synthesis of high-quality, drug-loaded biodegradable particles.

A mandatory outdoor experience program (MOEP), involving a three- to four-day outdoor canoe excursion, has been a compulsory university course for undergraduate students for nearly five decades at a post-secondary institution in Northern Ontario, Canada. However, the experiences and perspectives of students who participated in these excursions have not been fully investigated. The aim of this study was to harness the power of storytelling by alumni to improve our understanding of the long-term impact of MOEPs. Using an innovative methodology combining computer-assisted qualitative data analysis (Leximancer) and framing theory, the links between alumni stories became evident through three main interconnected frames: people, activity, and environment. Although there are unique components of the MOEP program described by our participants, the results contribute to the retrospective literature on the critical and memorable features that students recall years after completing an outdoor adventure experience.

The ability of humans to identify and reproduce short time intervals (in the region of a second) may be affected by many factors ranging from the gender of the individual observer, through the attentional state, to the precise spatiotemporal structure of the stimulus. The relative roles of these very different factors are a challenge to describe and define; several methodological approaches have been used to achieve this to varying degrees of success. Here we describe a new paradigm affording not only a first-order measurement of the perceived duration of an interval but also a second-order metacognitive judgement of perceived time. This approach, we argue, expands the form of the data generally collected in duration-judgements and allows more detailed comparison of psychophysical behaviour to the underlying theory. We also describe a measurement model which provides estimates of the variability of the temporal estimates and the metacognitive judgments allowing comparison to an ideal observer. We fit the model to data collected for judgements of 750ms (bisecting 1500ms) and 1500ms (bisecting 3000ms) intervals across three stimulus modalities (Visual, Audio & Audiovisual). This enhanced form of data on a given interval judgement and the ability to track its progression on a trial-by-trial basis offers a way of looking at the different roles that subject-based, task-based and stimulus-based factors have on the perception of time.

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Supplementary Figures S10-S20 and figure legends

Little is known of the geospatial architecture of individual cell populations in lung adenocarcinoma (LUAD) evolution. Here, we perform single-cell RNA sequencing of 186,916 cells from five early-stage LUADs and 14 multiregion normal lung tissues of defined spatial proximities from the tumors. We show that cellular lineages, states, and transcriptomic features geospatially evolve across normal regions to LUADs. LUADs also exhibit pronounced intratumor cell heterogeneity within single sites and transcriptional lineage-plasticity programs. T regulatory cell phenotypes are increased in normal tissues with proximity to LUAD, in contrast to diminished signatures and fractions of cytotoxic CD8+ T cells, antigen-presenting macrophages, and inflammatory dendritic cells. We further find that the LUAD ligand–receptor interactome harbors increased expression of epithelial CD24, which mediates protumor phenotypes. These data provide a spatial atlas of LUAD evolution, and a resource for identification of targets for its treatment.Significance:The geospatial ecosystem of the peripheral lung and early-stage LUAD is not known. Our multiregion single-cell sequencing analyses unravel cell populations, states, and phenotypes in the spatial and ecologic evolution of LUAD from the lung that comprise high-potential targets for early interception.This article is highlighted in the In This Issue feature, p. 2355

Supplementary Methods

Researchers in the field of face perception have long debated the extent to which we process faces holistically (as a whole) versus analytically (focusing on individual features). While some evidence suggests that faces are perceived holistically, research on the neural organization of the visual system and people's subjective experiences indicate that face parts can also be analyzed individually. This view is corroborated by observations of hierarchical object representation in which selective neural populations are fine-tuned to detect specific visual properties ranging from simple features to more complex combination of features. Thus, advances in theories of face perception are met with two major challenges: How can hierarchical face representations be used to integrate holistic and analytic encoding within the same framework? And how can the stages of face processing be integrated with higher-level cognitive processes, such as memory and decision-making, that are recruited during facial perception? We propose a novel computational framework termed the Modular Serial-Parallel Network (MSPN), which synthesizes several perceptual and cognitive approaches including memory representations, signal detection theory, rule-based decision-making, mental architectures (serial and parallel processing), random walks, and process interactivity. MSPN provides a computational modeling account of four stages in face perception: (a) representational (b) decisional, (c) logical-rule implementation, and (d) modular stochastic accrual of information and can account for both choice probabilities and response-time predictions. In a face classification task, MSPN showed an impressive ability in fitting choice response time distributions over other models. MSPN can be used as a tool for further development and refinement of hypotheses in face perception. The analysis of the model’s parameter values, estimated from data, can be used to explore distinct properties of the perceptual and cognitive processes engaged in both analytic and holistic encoding. We conclude by outlining how MSPN could be generalized to other perceptual and cognitive domains.

Aims To isolate and characterize fungi associated with diseased soybean seedlings in Midwestern soybean production fields and to determine the influence of environmental and edaphic factors on their incidence. Methods and Results Seedlings were collected from fields with seedling disease history in 2012 and 2013 for fungal isolation. Environmental and edaphic data associated with each field was collected. 3036 fungal isolates were obtained and assigned to 76 species. The most abundant genera recovered were Fusarium (73%) and Trichoderma (11.2%). Other genera included Mortierella, Clonostachys, Rhizoctonia, Alternaria, Mucor, Phoma, Macrophomina and Phomopsis. Most recovered species are known soybean pathogens. However, non-pathogenic organisms were also isolated. Crop history, soil density, water source, precipitation and temperature were the main factors influencing the abundance of fungal species. Conclusion Key fungal species associated with soybean seedling diseases occurring in several US production regions were characterized. This work also identified major environment and edaphic factors affecting the abundance and occurrence of these species. Significance and Impact of the Study The identification and characterization of the main pathogens associated with seedling diseases across major soybean-producing areas could help manage those pathogens, and devise more effective and sustainable practices to reduce the damage they cause.

Plasma biomarkers associated with respiratory failure (RF) following hematopoietic cell transplantation (HCT) have not been identified. Therefore, we aimed to validate early (7 and 14 days post-HCT) risk biomarkers for RF. Using tandem mass spectrometry, we compared plasma obtained at day 14 post-HCT from 15 patients with RF and 15 patients without RF. Six candidate proteins, from this discovery cohort or identified in the literature, were measured by enzyme-linked immunosorbent assay in day-7 and day-14 post-HCT samples from the training (n = 213) and validation (n = 119) cohorts. Cox proportional-hazard analyses with biomarkers dichotomized by Youden’s index, as well as landmark analyses to determine the association between biomarkers and RF, were performed. Of the 6 markers, Stimulation-2 (ST2), WAP 4-disulfide core domain protein 2 (WFDC2), interleukin-6 (IL-6), and tumor necrosis factor receptor 1 (TNFR1), measured at day 14 post-HCT, had the most significant association with an increased risk for RF in the training cohort (ST2: hazard ratio [HR], 4.5, P = .004; WFDC2: HR, 4.2, P = .010; IL-6: HR, 6.9, P < .001; and TFNR1: HR, 6.1, P < .001) and in the validation cohort (ST2: HR, 23.2, P = .013; WFDC2: HR, 18.2, P = .019; IL-6: HR, 12.2, P = .014; and TFNR1: HR, 16.1, P = .001) after adjusting for the conditioning regimen. Using cause-specific landmark analyses, including days 7 and 14, high plasma levels of ST2, WFDC2, IL-6, and TNFR1 were associated with an increased HR for RF in the training and validation cohorts. These biomarkers were also predictive of mortality from RF. ST2, WFDC2, IL-6 and TNFR1 levels measured early posttransplantation improve risk stratification for RF and its related mortality.

This paper traces the formation, dissemination, and impact of a corpus of narratives about an alchemical icon of the god Murukaṉ. It was purportedly crafted by Bhogar, a Siddhar-alchemist, at the Tamil temple site of Palani in ancient times. These narratives, beginning in the early twentieth century, asserted that any object coming into direct contact with the icon was imbued with miraculous healing properties. Such lore placed Palani as a unique pilgrimage site, attracting pilgrims from the world over, and stimulating its economy to an unprecedented degree, making it the second wealthiest temple in India. Eventually, the demand for icon-touched substances and the assertion of the icon’s healing properties reached its terminal limit, whereby the body of the god itself became available for sale, first as scrapings and then, in a complicated conspiracy of bait and switch, in its entirety. This article explores how recent myths respond to the challenges of late colonial modernity in the 1930s and Tamil identity politics in the twenty-first century.

Viral-based systems are a popular delivery method for introducing exogenous genetic material into mammalian cells. Unfortunately, the preparation of lentiviruses containing the machinery to edit the cells is labor-intensive, with steps requiring optimization and sensitive handling. To mitigate these challenges, we introduce the first microfluidic method that integrates lentiviral generation, packaging, and transduction. The new method allows the production of viral titers between 10

While the Commission did not adopt any Article 102 prohibition decisions in 2012, commitment proceedings under Article 9 of Regulation 1/2003 and public statements by senior officials shed some light on its likely analytical approach and future enforcement priorities.The General Court and Court of Justice upheld prohibition decisions in several important judgments, including in AstraZeneca, which establishes a new category of abuse consisting in the exclusionary misuse of regulatory proceedings.The Courts' rulings are broadly consistent with previous case law and/or the analytical approach described in the Commission's Guidance Paper, enhancing legal certainty for stakeholders and national competition authorities.

Dynein is the primary minus-end-directed microtubule motor [1]. To achieve activation, dynein binds to the dynactin complex and an adaptor to form the “activated dynein complex” [2, 3]. The protein Lis1 aids activation by binding to dynein and promoting its association with dynactin and adaptor [4, 5]. Ndel1 and its orthologue Nde1 are dynein and Lis1 binding proteins that help control where dynein localizes within the cell [6]. Cell-based assays suggest that Ndel1/Nde1 also work with Lis1 to promote dynein activation, although the underlying mechanism is unclear [6]. Using purified proteins and quantitative binding assays, we found that Ndel1’s C-terminal region contributes to binding to dynein and negatively regulates binding to Lis1. Using single-molecule imaging and protein biochemistry, we observed that Ndel1 inhibits dynein activation in two distinct ways. First, Ndel1 disfavors the formation of the activated dynein complex. We found that phosphomimetic mutations in Ndel1’s C-terminal domain increase its ability to inhibit dynein-dynactin-adaptor complex formation. Second, we observed that Ndel1 interacts with dynein and Lis1 simultaneously and sequesters Lis1 away from its dynein binding site. In doing this, Ndel1 prevents Lis1-mediated dynein activation. Our work suggests thatin vitro, Ndel1 is a negative regulator of dynein activation, which contrasts with cellular studies where Ndel1 promotes dynein activity. To reconcile our findings with previous work, we posit that Ndel1 functions to scaffold dynein and Lis1 together while keeping dynein in an inhibited state. We speculate that Ndel1 release can be triggered in cellular settings to allow for timed dynein activation.

The present study used Systems Factorial Technology (Townsend & Nozawa, 1995) to investigate how people combine dual cues in semantic memory search. Our aims were (a) to understand how cues interact during the process of semantic search in convergent thinking and (b) to determine how workload capacity (i.e. cue-processing efficiency) is related to search performance. In two experiments, participants completed a typical convergent thinking test and a word production task. The results revealed that: (a) collective evidence supports similar patterns in cue-combination strategy despite individual differences in workload capacity, and (b) there exists a negative correlation between workload capacity and performance on convergent thinking test. A potential explanation is that, for the creative individual, loading many candidate answers leads to consumption of substantial processing resources that obtains as low workload capacity but also allows creative individuals to switch more easily from one candidate to another so that there is a higher probability of successfully producing an answer within a limited time. Our results further imply that workload capacity is a significant factor for the semantic search process in convergent thinking and provides new insight on the model of semantic search and creativity. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cardiovascular disease is the leading cause of death worldwide, often associated with coronary artery occlusion. A common intervention for arterial blockage utilizes a vascular graft to bypass the diseased artery and restore downstream blood flow; however, current clinical options exhibit high long-term failure rates. Our goal was to develop an off-the-shelf tissue-engineered vascular graft capable of delivering a biological payload based on the monocyte recruitment factor C-C motif chemokine ligand 2 (CCL2) to induce remodeling. Bi-layered silk scaffolds consisting of an inner porous and outer electrospun layer were fabricated using a custom blend of Antherea Assama and Bombyx Mori silk (lyogel). Lyogel silk scaffolds alone (LG), and lyogel silk scaffolds containing microparticles (LGMP) were tested. The microparticles (MPs) were loaded with either CCL2 (LGMP+) or water (LGMP-). Scaffolds were implanted as abdominal aortic interposition grafts in Lewis rats for 1 and 8 weeks. 1-week implants exhibited patency rates of 50% (7/14), 100% (10/10), and 100% (5/5) in the LGMP-, LGMP+, and LG groups, respectively. The significantly higher patency rate for the LGMP+ group compared to the LGMP- group (p = 0.0188) suggests that CCL2 can prevent acute occlusion. Immunostaining of the explants revealed a significantly higher density of macrophages (CD68+ cells) within the outer vs. inner layer of LGMP- and LGMP+ constructs but not in LG constructs. After 8 weeks, there were no significant differences in patency rates between groups. All patent scaffolds at 8 weeks showed signs of remodeling; however, stenosis was observed within the majority of explants. This study demonstrated the successful fabrication of a custom blended silk scaffold functionalized with cell-mimicking microparticles to facilitate controlled delivery of a biological payload improving their in vivo performance. Statement of significance This study outlines the development of a custom blended silk-based tissue–engineered vascular graft (TEVG) for use in arterial bypass or replacement surgery. A custom mixture of silk was formulated to improve biocompatibility and cellular binding to the tubular scaffold. Many current approaches to TEVGs include cells that encourage graft cellularization and remodeling; however, our technology incorporates a microparticle based delivery platform capable of delivering bioactive molecules that can mimic the function of seeded cells. In this study, we load the TEVGs with microparticles containing a monocyte attractant and demonstrate improved performance in terms of unobstructed blood flow versus blank microparticles. The acellular nature of this technology potentially reduces risk, increases reproducibility, and results in a more cost-effective graft when compared to cell-based options.

A drug delivery system for the paranasal sinuses consisting of a freeze-dried thermoresponsive hydrogel with degradable microspheres, called FD-TEMPS (Freeze Dried—Thermogel, Extended-release Microsphere-based delivery to the Paranasal Sinuses), was developed. Glass transition temperatures (Tg′) of the maximally freeze concentrated solutions consisting of poly(N-isopropylacrylamide) (pNIPAAm) and polyethylene glycol (PEG) were determined by differential scanning calorimetry, which informed optimization of the thermogel formulation. By replacing low molecular weight (MW) PEG (200 Da) with a higher MW PEG (2000 Da), the resulting freeze-dried gel exhibited a brittle texture, porous structure, and low residual moisture (

Introduction Teleophthalmology has a natural role in the military due to the inherent organization of its medical system, which provides care to patients in remote locations around the world. Improving access to ophthalmic care enhances force readiness because ocular trauma and disease can cause vision impairment or blindness and can occur anywhere service members are located. Recently, a secure, Health Insurance Portability and Accountability Act–compliant mobile phone application (app) for teleophthalmology called Forward Operating Base Expert Telemedicine Resource Utilizing Mobile Application for Trauma (FOXTROT) was beta tested in Afghanistan and demonstrated that this solution can improve and extend ophthalmic care in a deployed environment. There are few civilian or military teleophthalmology solutions for ocular trauma and disease in an urgent or emergent ophthalmic care setting. Civilian teleophthalmology solutions have largely been developed for disease-specific models of care. In this work, we address this gap by testing the FOXTROT app in a non-deployed, emergent care setting. Materials and Methods We evaluated the use of the teleophthalmology mobile phone app (FOXTROT) in a non-deployed military setting at the Malcolm Grow Medical Clinics and Surgery Center at Joint Base Andrews in Maryland. Consults from the emergent care center were placed by providers using the app, and the on-call ophthalmologist responded with treatment and management recommendations. The primary outcomes were response within the requested time, visual acuity tested in both eyes, agreement between the teleophthalmology and the final diagnosis, and the number of communication or technical errors that prevented the completion of consults. The secondary outcomes were average response time and the number of consults uploaded to the medical record. Results From October 2020 to January 2022, 109 consults were received. Ten consults had communication or technical errors that prevented the completion of consults within the app and were excluded from the analysis of completed consults. Of the 99 completed consults, responses were given within the requested time in 95 (96.0%), with the average response time in 11 minutes 48 seconds (95% confidence interval, 8 minutes 57 seconds to 14 minutes 41 seconds). Visual acuity was tested in both eyes in 56 (56.6%). There was agreement between the teleophthalmology diagnosis and the final diagnosisin 40 of 50 (80.0%) consults with both a teleophthalmology and final diagnosis. Ninety-eight (99.0%) consults were uploaded to the patient’s medical record. Conclusions Beta testing of a teleophthalmology mobile phone app (FOXTROT) in a noncombat emergent care setting demonstrated that this solution can extend ophthalmic care in this environment at a military treatment facility. However, improvements in the reliability of the platform are needed in future developments to reduce communication and technical errors.

Graphical perception is a crucial part of scientific endeavour, and the interpretation of graphical information is increasingly important among the lay public, who are often presented with graphs of data in support of different policy positions. However, graphs are multidimensional and data in graphs are comprised not only of overall global trends but also local perturbations. We presented a novel function estimation task in which scatterplots of noisy data that varied in the number of data points, the scale of the data, and the true generating function were shown to observers. Observers were asked to draw the function which they believe generated the data. Our results indicated not only a general influence of various aspects of the presented graph (e.g., increasing the number of data points results in smoother generated functions), but also clear individual differences, with some observers tending to generate functions which track the local changes in the data and others following global trends in the data.

We present a novel "on-off", cost-effective, rapid electrochemical aptasensor combined with a microfluidics cartridge system for the detection of Δ

The use of information technologies for the public interest, such as COVID-19 tracking apps that aim to reduce the spread of COVID-19 during the pandemic, involve a dilemma between public interest benefits and privacy concerns. Critical in resolving this conflict of interest are citizens’ trust in the government and the risks posed by COVID-19. How much can the government be trusted to access private information? Furthermore, to what extend do the health benefits posed by the technology outweigh the personal risks to one's privacy? We hypothesize that citizens’ acceptance of the technology can be conceptualized as a calculus of privacy concerns, government trust, and the public benefit of adopting a potentially privacy-encroaching technology. The importance that citizens place on their privacy and the extent to which they trust their governments vary though out the world. The present study examined the public’s privacy calculus across nine countries (Australia, Germany, Italy, Japan, Spain, Switzerland, Taiwan, the United Kingdom, and the United States) focusing on social acceptance of contact-tracing technologies during the COVID-19 pandemic. We found that across countries, privacy concerns were negatively associated with citizens’ acceptance of the technology, while government trust, perceived effectiveness of the technology, and the health threats of COVID-19 were positively associated. National cultural orientations moderate the effects of the basic factors of privacy calculus. In particular, individualism (value of the individual) amplified the effect of privacy concerns, whereas general trust (trust in the wider public) amplified the effect of government trust. National culture therefore requires careful attention in resolving public policy dilemmas of privacy, trust, and public interest.